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• Four genera of the South African Amaryllidaceae surveyed for the period 2013–2020. • These include representatives of Crinum, Ammocharis, Amaryllis and Cyrtanthus. • Shown to have a notable presence in South African traditional medicine. • Such indigenous knowledge systems guide pharmacological evaluation of target species. • Significant findings made in the cancer and motorneuron disease arenas. The plant family Amaryllidaceae has attracted widespread attention in view of the interesting biological properties of its alkaloid principles. Many of these discoveries are based on the traditional usage of its members in regions where they are prominent. Over a third of its complement is found in southern Africa, hence the heightened interest in the Amaryllidaceae from this territory. Up to 2012, over 80 species were examined, mainly for their alkaloid constitution. Given the medicinal potential of the family as well as its widespread usage in South African traditional medicine, efforts over the past decade have intensified in understanding its biological properties. This account focuses on the biological activities that have been reported since 2013 for extracts of four genera of the South African Amaryllidaceae, viz Crinum, Ammocharis, Amaryllis and Cyrtanthus. Fourteen related species were assayed during this period, with Crinum (5 species) and Cyrtanthus (6 species) affording the bulk of the targets. Although most studies utilized the bulbous extracts, there were some instances involving the use of root, leaf and flower materials. The extractants used ranged from water to hexane, with a few examples addressing the outcomes of environmentally-benign extraction procedures. Close to twenty different areas were identified wherein the biological properties of the extracts were examined including, cytotoxicity, AChE and BuChE inhibition, cardio and hypertensive effects, antioxidant and anti-inflammatory effects, as well as antibacterial, antifungal and antiparasitic effects. Some studies also probed the mechanistic basis to these activities, notably in regards to their cytotoxic and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

• South Africa affords a rich and diverse source of Amaryllidaceae plant species. • Boophone, Nerine, Brunsvigia, Strumaria and Crossyne well-represented in the region. • This survey covers biological studies of these five genera for 2013–2020. • Around 20 areas identified in which their extracts have been probed for such effects. • Traditional usage of several of the representative species is also highlighted. The presence of plants in human health and well-being has been trenchant since time immemorial. Some of the most crucial medicines in use today are derived from plant-based materials. Traditional plant usage has played a pivotal role in guiding many of the discoveries that were accomplished in the clinical realm. The plant family Amaryllidaceae is recognized for its interesting biological properties, notably in the areas of cancer and motorneuron disease therapeutics. Its members are well-represented in South Africa, with a proliferation hub centered over its Western Cape Province. Boophone, Nerine, Brunsvigia, Strumaria and Crossyne are genera of the Amaryllidaceae that are prominent amongst the local floral biodiversity. Previous reviews on the biological action of these genera were up to date until 2012. The present account is an update of the field covering material published between 2013 and 2020. It examines the plant parts studied, the solvents utilized in the extraction procedures as well as the biological assays against which the extracts have been screened. These were seen to involve antimicrobial, anti-inflammatory, antioxidant, anticancer, anticholinesterase, cardiovascular, hypertensive and anxiolytic effects. Studies were also identified which addressed the herbicidal and insecticidal effects of some of the plants. Some efforts focused on the molecular basis to the biological activities, notably in regards to anti-inflammatory and anticancer action as well as to motorneuron-related effects. Significant effort is made throughout the text to emphasize the traditional medicinal usage and how such indigenous knowledge has guided the biological evaluation of the plants. [ABSTRACT FROM AUTHOR]

Members of the plant family Amaryllidaceae are widely recorded in traditional systems of medicine. Their usage for inflammatory conditions is most prominent, with substantive evidence emerging from several locations around the world. This survey was undertaken to identify such plant taxa, highlight the countries from which they originate and afford details of the ailments against which they are utilized. The undertaking also sought to establish the in vitro and in vivo activities of Amaryllidaceae plant extracts in inflammation-based assays. Furthermore, it set out to unravel the molecular mechanisms used to explain these effects. Over six-hundred articles were identified in searches carried out on SciFinder, Scopus, ScienceDirect, PubMed and Google Scholar. These were condensed to around 170 that formulated the basis of the text. The keyword engaged was 'Amaryllidaceae' in conjunction with 'inflammation' or 'anti-inflammatory', as well as the names of individual genera combined with the latter two. Fifty-one species from thirty-five countries were identified for their uses against inflammation. Twenty-four of such conditions were discernible, of which their applicability in wound healing and pain management was most conspicuous. The utilization of all plant parts was apparent, preparations of which were used primarily via topical application. Extracts of seventy-three species (from twenty-three genera) were examined in nearly thirty inflammation-based assays where their activities in vitro and in vivo were shown to be significant. They were effective in vivo against pain and swelling as well as wound healing, without detriment towards test subjects. The in vitro studies were carried out mainly in mononuclear cells such as macrophages, leukocytes, lymphocytes and neutrophils against which their cytotoxic effects were seen to be minimal. The modes of operation were shown to involve modulation of both pro-inflammatory (such as NF-κB, TNF-α, IL-6, IFN-γ, COX and NO) and anti-inflammatory (such as IL-10) factors. The Amaryllidaceae is showcased as a platform highly conducive towards studies in the inflammation arena. Potent activities in instances were observed via in vitro and in vivo models of study, bolstered by the significant amounts of information emerging from traditional forms of medicine. It is conceivable that the family may yield future anti-inflammatory chemotherapeutics, particularly those related to its alkaloid principles. [Display omitted] • Fifty-one Amaryllidaceae species recorded worldwide for uses against inflammation. • Utilized most for wound healing, pain management and general inflammation purposes. • Extracts of seventy-three species have been examined in inflammation-related assays. • Good activities described from in vitro and in vivo models of study. • Effects manifested via modulation of both pro- and anti-inflammatory factors. [ABSTRACT FROM AUTHOR]

• Five genera of the South African Amaryllidaceae surveyed for the period 2013–2020. • These are inclusive of Crinum, Ammocharis, Amaryllis, Cyrtanthus and Brunsvigia. • Around 90 isoquinoline alkaloids and 25 non-alkaloidal entities described. • Chemosystematics of selected alkaloids considered. • Biological properties of isolated compounds also described. There is considerable interest in the plant family Amaryllidaceae for its biologically-active isoquinoline alkaloid principles. Some of these (such as galanthamine and narciclasine) have demonstrated their applicability in the clinical arena, particularly as cancer and motorneuron disease therapeutics. While synthetic organic chemistry affords ideal opportunities for drug development with such targets, the phytochemical approach is considered a somewhat more amenable option. In this regard, southern Africa has garnered widespread attention due to the abundance of Amaryllidaceae plants in its territory. Crinum, Ammocharis, Amaryllis, Cyrtanthus and Brunsvigia are genera of the family that are likewise well-represented in southern Africa. Up to 2012, thirty members from these genera were examined for their chemical and biological properties, culminating with the identification of nearly one-hundred alkaloid entities several of which exhibited notable biological activities. The present effort covers studies since 2013 that have been undertaken on the title genera in regards to their chemical and biological characteristics. Close to ninety alkaloids and twenty-five non-alkaloid entities were described during this time-frame from fifteen representative species. Biological studies included cholinesterase inhibiton, cytotoxicity, antidiabetes and antihypertensive effects, herbicidal, insecticidal and plant growth regulatory effects, as well as anti-inflammatory, antioxidant and antiplasmodial effects. The structural variety of the compounds isolated in cases allowed for structure-activity probes to be made in some of the assays. There were also studies carried out to establish the molecular basis to these activities, notably in the area of molecular cancer chemotherapeutics. [ABSTRACT FROM AUTHOR]

• Tazettine alkaloids of the Amaryllidaceae surveyed for cytotoxic activities. • Eleven of such entities examined in nearly 20 different types of cancers. • Cytotoxicity assays carried out against around 50 different cancer cell lines. • Structural elements of tazettine alkaloids are significant in their activities. • Multidimensional molecular basis to cytotoxicity of tazettine alkaloids uncovered. From camptothecin to vinblastine, plant alkaloids continue to capture the imagination of scientists as a valuable source of anticancer drugs. Given that they are also amongst the most common secondary metabolites encountered in plants, the number of alkaloid entities subjected to cytotoxicity evaluations now runs into several thousands. Interest in the plant family Amaryllidaceae has been persistent owing to the potent cytotoxic activities of several of its isoquinoline alkaloid principles. This survey is an indepth account of such properties discernible for tazettine alkaloids belonging to the minor alkaloid groups of the Amaryllidaceae. Eleven of such compounds have up to now been screened against around 50 cancer cell lines which may be classified into nearly 20 different types of cancers. Although the activities in most instances were moderate to mild, notable responses were observed against some leukemia, adenocarcinoma, lymphoma and glioblastoma cell lines. In fact, pretazettine (ED 50 0.3 μg/mL) was amongst the most potent of all Amaryllidaceae alkaloids screened against the human Molt4 T-lymphoma cell line. To most accounts, the parent compounds (such as tazettine and pretazettine) with their distinct ring systems and substitution patterns exhibit the best activities, offering little space for structural adjustments via semi-synthetic operations. Several avenues have been probed in attempts to elucidate the mechanisms by which tazettine alkaloids manifest their cytotoxic effects including, inhibition of protein synthesis, apoptosis and efflux pump interactions, the first of which to date offers the most profound insights. [ABSTRACT FROM AUTHOR]

• A review of the cytotoxic homolycorine alkaloids of the Amaryllidaceae is presented. • Forty-two of such compounds have to date been screened against 62 cancer cell lines. • Best activity observed for lycorenine against HepG2 hepatoma cells (ED 50 1.2 μg/mL). • Modification of the homolycorine nucleus affords useful insight to cytotoxicities. • Topoisomerase inhibition identified as a key reaction in mechanistic pathways. Stimulated by the promising results seen for its phenanthridones in clinical trials, interest in the Amaryllidaceae as a potential source of anticancer drugs has intensified in recent years. As such, over three hundred isoquinoline principles from its various alkaloid groups have to date been screened against a large number of cancer cell lines. Whilst significant effort has been diverted towards studies of lycorine and its congeners, the closely-allied homolycorine alkaloids of this plant family have largely been overlooked. These compounds have often been used as supporting acts to bolster the diversity of structures in cytotoxicity studies of the more recognized phenanthridone, lycorane and crinane alkaloids of the Amaryllidaceae. This notwithstanding, a substantial amount of information has surfaced over the past several years on such effects for the homolycorine alkaloids. This review takes a detailed look at the cytotoxic effects manifested by over forty of these alkaloids against around sixty cell lines, which may be classified into eighteen different types of cancers. In this regard, good activities were detected for some constituents (such as lycorenine and hippeastrine) against various hepatic and prostate cancers. The structural features which support and fortify the efficacy of the homolycorine alkaloid cytotoxic pharmacophore are also considered. These include the ways in which the innate ring systems are appended as well as the size, geometry and electronics of the attendant substituents. In addition, the various mechanisms used to rationalize the cytotoxic responses are described notably, interaction with DNA, apoptosis induction, protection from tumor invasion, efflux pump perturbation and topoisomerase inhibition. [ABSTRACT FROM AUTHOR]

The objective of the paper is to develop a new method to model the manufacturing cost–tolerance and to optimize the tolerance values along with its manufacturing cost. A cost–tolerance relation has a complex nonlinear correlation among them. The property of a neural network makes it possible to model the complex correlation, and the genetic algorithm (GA) is integrated with the best neural network model to optimize the tolerance values. The proposed method used three types of neural network models (multilayer perceptron, backpropagation network, and radial basis function). These network models were developed separately for prismatic and rotational parts. For the construction of network models, part size and tolerance values were used as input neurons. The reference manufacturing cost was assigned as the output neuron. The qualitative production data set was gathered in a workshop and partitioned into three files for training, testing, and validation, respectively. The architecture of the network model was identified based on the best regression coefficient and the root-mean-square-error value. The best network model was integrated into the GA, and the role of genetic operators was also studied. Finally, two case studies from the literature were demonstrated in order to validate the proposed method. A new methodology based on the neural network model enables the design and process planning engineers to propose an intelligent decision irrespective of their experience. [ABSTRACT FROM AUTHOR]

Malaria is prevalent in tropical and subtropical regions of the globe. With over 200 million cases reported annually, particularly in sub-Saharan Africa, it is an unnecessary burden to already overworked and ailing healthcare structures. Traditional medicine (TM) remains vibrant in most of these regions wherein plants often serve as the first line of defense against malaria. Given this fact as well as the successes elsewhere of therapies such as Artemisia annua emanating from evidence-based TM, interest in plants as a source of new antimalarial drugs has been rejuvenated. The bulbous plant family Amaryllidaceae is recognized for its structurally-diverse alkaloid constituents which exhibit interesting biological properties. This review focuses on the in vitro activities demonstrated by its crinane alkaloids against various strains of the malaria-causing parasite Plasmodium falciparum. The survey embraces the twelve genera of the Amaryllidaceae whose nineteen representative species have been examined for antiplasmodial crinane alkaloid principles. A total of seventy-two compounds were screened against nine strains of P. falciparum , with the α -crinanes reflecting better overall activities than their corresponding β -crinane subgroup congeners. In terms of potency, an ED 50 of 0.14 μg/mL (for augustine in the D-6 strain) and IC 50 of 0.35 μg/mL (for haemanthidine in the K1 strain) were the lowest activity indices observed. Structure-activity relationship studies afforded useful insight on the antiplasmodial pharmacophore and the features supporting its efficacy. Overall, crinane alkaloids have provided a useful platform for the study of antiplasmodial effects, not only in terms of potency but also in terms of structural diversity. The Amaryllidaceae as a source of antiplasmodial crinane alkaloid constituents. Jerald J. Nair, Johannes van Staden. Unlabelled Image • The Amaryllidaceae provides an abundant source of antiplasmodial constituents. • Nineteen species examined for antiplasmodial alkaloids. • Seventy-two crinane alkaloids screened against various Plasmodium falciparum strains. • Activities detected across both chloroquine sensitive and resistant strains. • Haemanthamine and haemanthidine identified with best overall activities. • Haemanthidine (IC 50 0.35 μg/mL) better than mefloquine (IC 50 3.94 μg/mL) in K1 strain. [ABSTRACT FROM AUTHOR]

Traditional Geometric tolerance allocation method assumes the parts of the assembly are purely rigid. Upon assembly and function, it is realised that the rigidity of the parts is non-ideal which leads to severe variations. Hence the performance of an assembly declines and is associated with the parts performance in the assembly. An assembly always experiences deformations due to internal and external forces/loads and drop in efficiency is critically observed. This paper proposes a methodology to predict such variations in assembly and integrate geometric tolerance design to it. First, the Ontological model of the assembly is predicted through Finite Element Analysis, and the near net shape of the assembly is obtained. Second, a set of features of an assembly which plays a vital role is selected, to determine the optimal geometric tolerances through the hybridised neural network and Genetic algorithm. Finally, a gear pump assembly is chosen, the proposed method is demonstrated. This method will be useful for design and new product development engineers in reducing the assembly variations and associated manufacturing cost. [ABSTRACT FROM AUTHOR]

Abstract The birth, growth, proliferation and death of cells involve a rigorous and continuous process in place to ensure the survival of living organisms. The cell cycle prevails at the core of this process to facilitate the division of a parent cell as well as the duplication of its genetic matter. Although checkpoints exist to steer the course of a cell from one phase to the other, malfunctions at any point of the four active phases of the cell cycle can have detrimental effects. Cancer is thought to be a consequence of such a malfunction in the cell cycle which endows a cell with enhanced replicative potential, immunity to anti-growth signals and the ability to evade apoptosis. This characteristic has been exploited in cancer chemotherapy since a significant number of anticancer drugs manifest their action via cell cycle modulatory effects. The plant family Amaryllidaceae is distinguished for its alkaloid principles which exhibit potent (at the sub-nanomolar level in some cases) and cell line specific antiproliferative activities, with apoptosis induction a key feature of these properties. As a consequence there has been sustained interest in these chemical entities as a source of new anticancer drugs. This has been matched by the large body of work that has emerged over the past two decades addressing their cytotoxic potential, establishing a structure-activity relationship basis as well as probing their mode of action. This review focuses on studies which highlight how Amaryllidaceae alkaloids modulate the cell cycle of cancer cells. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

There is a pressing need in antibiotic drug discovery for new drugs to counterbalance the effects of multidrug resistance. Plants represent a viable platform for such endeavors owing to their traditional relevance in infectious disease therapies as well as their vast chemical resources. As many as fifty different species of the Amaryllidaceae are discernible with such functions in traditional medicine, thirty-nine of which have been subjected to pharmacological evaluations. Submicromolar antibacterial activities for several of these plants have been the driving force behind studies targeting their active constituents. This review accounts for close to a hundred of such entities, mainly isoquinoline alkaloids, which have been the focus in assays of thirty different bacterial pathogens. Promising activities were detected in several instances, although disappointingly the submicromolar level could not be breached. Also considered are structure–activity relationships which have emerged within the various groups of Amaryllidaceae alkaloids. [ABSTRACT FROM AUTHOR]

In Computer Aided Process Planning (CAPP), process parameters selection for the given manufacturing feature is the final activity and it is the key area for research and development. In this work, an attempt has been made to optimize parameters for micro end-milling operation as a part of CAPP system development for micromachining processes using Artificial Intelligence (AI) approach. Genetic Algorithm (GA) has been found to be the robust and efficient tool to solve nonlinear optimization problems involved in process planning. Microfeatures of size 0.7 and 1 mm are considered and polymethyl methacrylate is chosen as the work material due to its potential application in microparts fabrication. Initially, experimental investigation has been carried out to analyze the impact of process conditions such as spindle speed and feed rate on surface roughness and machining time. Further multiobjective optimization for minimization of responses is carried out using GA. Finally, confirmation experiments are carried out to validate the accuracy of GA results. The optimized process parameters are stored in the database and it ensures foolproof parameters for micro end-milling operation for CAPP applications apart from manuals and catalogues. The proposed approach can be repeated for various other end mill features and for different work and tool material combination to ensure a complete parameters selection module for CAPP system applications. [ABSTRACT FROM AUTHOR]

The family Amaryllidaceae has been documented in traditional systems of medicine around the globe. Its member tribe Haemantheae occurs chiefly in South Africa, where around twenty of its species are identifiable with a wide variety of functions in such practices. This account details work published from 2013 to 2020 on the tribe Haemantheae involving Clivia , Cryptostephanus , Haemanthus , Scadoxus and Gethyllis. Focus is maintained on the traditional medicinal aspects, pharmacological activities and identification of the active principles. Significant effort is also made to outline the molecular basis to some of these effects. The major search engine platforms including, SciFinder, Scopus, ScienceDirect, PubMed and Google Scholar were utilized at the literature consolidation stage. Keywords engaged in the process included 'Amaryllidaceae' and 'Haemantheae' as well as individual genera and specie names. Twenty-four species of the five genera were encountered over the designated time frame. New traditional medicinal information has emerged on nine of these species, where usage ranged from the treatment of wounds and infections, circulatory and gastrointestinal issues to AIDS and TB. Significant amounts of new data also appeared in relation to the antimicrobial, anti-inflammatory, antioxidant, anticholinesterase, antidepressive and cytotoxic effects of these plants. Potent activities were observed in some instances, as they were in regards to the anti-inflammatory effects of some Gethyllis species in their cyclooxygenase-inhibitory effects. The entities behind these activities, with few exceptions, were shown to be isoquinoline alkaloids which are known to dominate the chemistry of the Amaryllidaceae. Interesting observations were also made for the mechanisms behind some of the effects, notably in the inflammatory and motorneuron disease arenas. The tribe Haemantheae has proved to be a rich and diverse platform for studies of the Amaryllidaceae in the key areas of traditional medicine, pharmacology and phytochemistry. Indigenous knowledge has played a significant role in guiding the biological evaluations, while identification of the active principles has been bolstered by the exceedingly rich alkaloid diversity of the Amaryllidaceae. As such, Haemantheae should continue to feature prominently in drug discovery efforts targeted at the family. [Display omitted] • The tribe Haemantheae of the South African Amaryllidaceae surveyed from 2013 to 2020. • Genera represented are Clivia , Cryptostephanus , Haemanthus , Scadoxus and Gethyllis. • Traditional usage, pharmacology and bioactive constitution aspects are covered. • Anticancer, antimicrobial and anti-inflammatory are some of the effects described. • Insight also afforded to the molecular basis to some of the activities. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Boophone disticha is the most common member of the South African Amaryllidaceae used extensively in traditional medicine of the various indigenous population groups, including the Sotho, Xhosa and Zulu as well as the San. This survey was carried out to identify and highlight areas relevant to the traditional usage of Boophone disticha. Pharmacological aspects were examined with the purpose of reconciling these with the traditional usage of the plant. In relation to phytochemical make-up, particular attention was paid on how its alkaloid constitution might corroborate the various biological effects manifested by the plant. Materials and methods: Information gathering involved the use of four different database platforms, including Google Scholar, ScienceDirect, SciFinder® and Scopus. Arrangement and detailing of this information is as reflected in the various sections of the paper. Results: Sixteen categories were identified under which Boophone disticha finds use in traditional medicine. These were shown to include general usage purposes, such as ‘cultural and dietary’, ‘well-being’, ‘personal injury’, ‘divinatory purposes’, ‘psychoactive properties’ and ‘veterinary uses’. Furthermore, traditional usage was seen to involve six body systems, including functions pertaining to the circulatory, gastrointestinal, muscular, neurological, respiratory and urinary systems. The four remaining categories relate to use for inflammatory conditions, cancer, malaria and tuberculosis. Overall, three areas were discernible in which Boophone disticha finds most usage, which are (i) ailments pertaining to the CNS, (ii) wounds and infections, and (iii) inflammatory conditions. In addition, several aspects pertaining to the toxic properties of the plant are discussed, including genotoxicity, mutagenicity and neurotoxicity. Conclusion: The widespread ethnic usage of Boophone disticha has justified its standing as a flagship for the Amaryllidaceae and its relevance to South African traditional medicine. Furthermore, its promising pharmacological and phytochemical profiles have stimulated significant interest in the clinical realm, especially in the areas of cancer and motor neuron disease chemotherapy. These collective properties should prove useful in steering the progress of the plant towards a wider audience. [ABSTRACT FROM AUTHOR]

Abstract: Several of the Amaryllidaceae alkaloids are known for their cytotoxic properties, of which the lycorine group representatives are prominent for potent and cell line specific antiproliferative activities. As a distinct niche within the lycorine group, the phenanthridones, exemplified by narciclasine and pancratistatin, have shown much promise as remarkably selective cytotoxic agents and are presently at various stages of development, with a clinical candidate likely to appear on the market within the next decade. The crinane group of the Amaryllidaceae has also spawned several molecules, such as crinamine and haemanthamine, with promising cytotoxic activities. In the present study, the β-crinane distichamine as well as the phenanthridone narciprimine, both rare constituents of the Amaryllidaceae, are revealed as novel antiproliferative agents. Apoptosis-inducing effects are demonstrated for distichamine in human acute lymphoblastic leukemia (CEM) cells. These findings provide further insights to the structural details of the apoptosis-inducing pharmacophores resident within both series of alkaloids. [Copyright &y& Elsevier]

Abstract: Cycads are a group of slow-growing, perennial, dioecious plants which in geological times thrived during the Mesozoic era. The present worldwide complement of around 300 species is distributed through both tropical and subtropical regions of the globe, and has pronounced centres in Australia, Mexico and South Africa. These popular plants are known for their ornamental, economic, dietary and medicinal value. However, increased demand collectively from this sector, as well as decimation of large tracts of cycad populations in the wild through habitat destruction and unscrupulous collection, has precipitated a fragile conservation status for the family, with majority of its species listed as threatened by statutory bodies such as CITES and IUCN. Despite their popularity, cycads have for several centuries been known to be toxic. The plants have been shown to have carcinogenic, mutagenic, teratogenic and neurotoxic properties, and its major constituent principles macrozamin and cycasin have exhibited similar effects in model studies. Cycads are used widely in traditional medicine (TM) in South Africa and the majority of endemic species are commonly traded on local TM markets. The present study deals with the isolation of macrozamin from seed kernels of Encephalartos transvenosus and quantification of this toxic methylazoxymethanol (MAM) glycoside via HPLC in selected indigenous species. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Boophone disticha (Amaryllidaceae) is one of the most common bulbous plants used for medicinal purposes by the indigenous people of southern Africa. Its use as a narcotic substance by the Khoi/San tribes has been known for several centuries, while the Sotho, Xhosa and Zulu people are known to use the plant to treat a host of ailments, including inflammation, wounds, gynaecological conditions and psychosis. Aim of the study: Much of the pharmacological work on the plant, such as affinity to the serotonin transporter, has been based on its reputed usage for narcotic purposes. However, its widespread use to treat wounds and infections has not been linked to a specific chemical entity. In this regard, Boophone disticha was here examined for its phytochemical composition which could shed light on the use of the plant for such purposes. Materials and methods: The known crinane alkaloids buphanidrine and distichamine were isolated via column chromatography of the ethanolic extract of bulbs of Boophone disticha. Structural details of the compounds were determined by high field 2D NMR and mass spectroscopic techniques. Microbial activity against selected Gram-positive and Gram-negative bacteria was ascertained according to the micro-dilution assay. Results: Both buphanidrine and distichamine were uncovered as novel, broad spectrum moderately active, antibacterial agents with the best MIC value detected at 0.063mg/ml for Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. MIC values for Bacillus subtilis were two-fold less than that observed for the other three bacteria, suggesting that the extract and pure compounds were selective in their interaction with the bacterial pathogens. Conclusion: Phytochemical investigation of Boophone disticha has led to the identification of two known crinanes, buphanidrine and distichamine. Based on the reputed traditional use of the plant for wounds and infections, both compounds were screened for antibacterial activity which revealed them to be novel, broad spectrum antibacterial agents with the best MIC value set at 0.063mg/ml. Their close structural similarity may have bearing on their similar activity profiles. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Boophone disticha (Amaryllidaceae) is one of the most common bulbous plants used for medicinal purposes by the indigenous people of southern Africa. Its use as a narcotic substance by the Khoi/San tribes has been known for several centuries, while the Sotho, Xhosa and Zulu people are known to use the plant to treat a host of ailments, including inflammation, wounds, gynaecological conditions and psychosis. Aim of the study: Much of the pharmacological work on the plant, such as affinity to the serotonin transporter, has been based on its reputed usage for narcotic purposes. However, its widespread use to treat wounds and infections has not been linked to a specific chemical entity. In this regard, Boophone disticha was here examined for its phytochemical composition which could shed light on the use of the plant for such purposes. Materials and methods: The known crinane alkaloids buphanidrine and distichamine were isolated via column chromatography of the ethanolic extract of bulbs of Boophone disticha. Structural details of the compounds were determined by high field 2D NMR and mass spectroscopic techniques. Microbial activity against selected Gram-positive and Gram-negative bacteria was ascertained according to the micro-dilution assay. Results: Both buphanidrine and distichamine were uncovered as novel, broad spectrum moderately active, antibacterial agents with the best MIC value detected at 0.063mg/ml for Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. MIC values for Bacillus subtilis were two-fold less than that observed for the other three bacteria, suggesting that the extract and pure compounds were selective in their interaction with the bacterial pathogens. Conclusion: Phytochemical investigation of Boophone disticha has led to the identification of two known crinanes, buphanidrine and distichamine. Based on the reputed traditional use of the plant for wounds and infections, both compounds were screened for antibacterial activity which revealed them to be novel, broad spectrum antibacterial agents with the best MIC value set at 0.063mg/ml. Their close structural similarity may have bearing on their similar activity profiles. [Copyright &y& Elsevier]

Abstract: The discovery of a novel five-component 1,2,3-triazole-containing pharmacophore that exhibits potent and selective inhibition of aromatase (CYP 450 19A1) is described. All compounds are derived from an initial aldol reaction of a phenylacetate derivative with an aromatic aldehyde. Structure–activity data generated from both syn- and anti-aldol adducts provides initial insights into the requirements for both potency and selectivity. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Plants of the family Amaryllidaceae are used widely in traditional medicine in South Africa. Several of these, including representatives of the genus Cyrtanthus find use in the treatment of mental illness and age-related dementia. Aim of the study: Based on the distribution of central nervous system-activating alkaloidal constituents within the genus Cyrtanthus, Cyrtanthus contractus was here explored for such compounds which could interact with acetylcholinesterase (AChE), of significance in the progression of neurodegeneration associated with Alzheimer''s disease. Materials and methods: The known phenanthridone alkaloid narciprimine was isolated via column chromatography of the ethanolic extract of bulbs of Cyrtanthus contractus. The structure of the compound was determined by high field 2D NMR and mass spectroscopic techniques. The classical method of Ellman et al. was used in the determination of AChE inhibitory activity. Results: The isolation of narciprimine from Cyrtanthus contractus is a landmark find since it has previously only been identified in Zephyranthes, Narcissus and Lycoris, genera endemic to the Americas, Europe and Asia, respectively. Narciprimine exhibited micromolar inhibitory activity (IC50 78.9) against the enzyme acetylcholinesterase. Conclusion: This work represents the first isolation of narciprimine from an African Amaryllidaceae species, which may be of chemotaxonomic significance. The AChE inhibitory activity of narciprimine, taken together with activities of other structurally similar inhibitors within the series affords further insight to the structural details of the lycorine alkaloid acetylcholinesterase inhibitory pharmacophore. [Copyright &y& Elsevier]

Most water management studies concentrate on the inter-temporal allocation problem or, more recently, spatial dynamics – but not both. While early spatial–temporal studies focused on the allocation of water quantity, this paper presents an approach to water quality analysis that incorporates both spatial and temporal dynamics in a watershed framework. The acid mine drainage (AMD) problem in the Cheat River watershed of West Virginia, USA, serves as a case study and provides an opportunity to test the modeling approach developed. The empirical models are written in General Algebraic Modeling System (GAMS) and solved using the CPLEX mixed integer programming package. The results suggest that available investments should be concentrated in heavily impaired stream segments. The model can be used to assess the economic implications of alternative watershed Total Maximum Daily Load (TMDL) implementation or other management strategies. [Copyright &y& Elsevier]

Fiber reinforced sandwich structures typically respond very poorly to transverse impact events. This paper is an attempt to investigate the impact response of sandwich panels subjected to low-velocity impact. Experimental investigations were carried out on the influence of three design factors: height of fall, core thickness, and impactor mass, which are the most relevant parameters to be considered for deflection. The study of behavior of the mentioned response was done by using Design of Experiments tool. Response surface methodology (RSM), a sequential experimentation strategy for model building, is used to model the response in order to determine the most significant factor among the influential factors. In this case, full factorial face-centered central composite design was chosen due to the number of factors and their levels in the study. The specimen consisted of face sheets made up of bi-woven glass fiber cloth with polyurethane foam as core material. The parametric analysis reveals that deflection increases steadily with an increase in the height of fall when compared with the impactor mass and the core thickness. The reason for this study is imperative for the next generation aircraft, marine, road, and rail vehicles with improved lightweight stiff materials that can absorb higher impact energy with higher resistance to deflection. [ABSTRACT FROM AUTHOR]

Abstract: This work presents the results of an experimental investigation concerning the low-velocity impact behavior of woven glass fiber epoxy matrix composite laminates. Experimental test were performed according to ASTM standards using an instrumented falling weight impact testing machine. Impact test were conducted to characterize the type and extent of the damage observed in laminate for range of thickness subjected to different impact velocities. Correlation of the residual indentation of the impacted specimens provides a criterion for the extent of the damage. As the impact energy was increased, the samples experienced one of two types of damages: a crack from the center of the laminate to the edge, or significant damage consisting of a dent localized in the region of impact. The history of relevant kinematical, dynamic and energetic quantities, both to synthesize the dependency of the energy parameters and force threshold values on the impact velocity are discussed. [Copyright &y& Elsevier]

Abstract: The synthesis of differentially functionalized analogs of the Amaryllidaceae alkaloid lycorine, accessed via a concise chemoselective silylation strategy, is described uncovering two of the most potent inhibitors of acetylcholinesterase (AChE) identified to date in this series. Important elements of this novel pharmacophore were elucidated through structure–activity relationship (SAR) studies. [ABSTRACT FROM AUTHOR]

Abstract: The watershed characterization and modeling system (WCMS) was developed to support decision making and the management of water resources at a statewide level in West Virginia. Specific hydrological analysis functions were combined within a customized GIS interface to provide decision support capabilities to both technical and non-technical users. Components of the current system include: an overland flow path model that indicates optimum water quality sampling locations, flow estimation for all streams in an identified area, an instream water quality and loading model for pollutant levels, and a ranking model to prioritize treatment alternatives based on user defined criteria and preferences. The primary goals of this system are to provide consistent technical information related to natural watershed processes and to predict the impacts of alternative management scenarios for decision makers. WCMS is currently used by the West Virginia Department of Environmental Protection (WVDEP) to guide policy development and management decisions that address watershed and water quality issues throughout the state. [Copyright &y& Elsevier]

Abstract: seco-Derivatives of the anticancer agent pancratistatin bearing the 2S,3S,4S,5S configuration were accessed via a novel, highly diastereoselective anti-aldol reaction. Structure–activity relationships reveal important insights into the seco-pancratistatin pharmacophore as a potent and selective inhibitor of human cytochrome P450 3A4 (CYP3A4), and highlight features of concern in advancing a potent, selective anticancer agent in the pancratistatin series. [Copyright &y& Elsevier]

Abstract: An investigation of the constituents in heartwood and resin of Prunus avium is reported. A mini-library of structurally diverse flavanones and flavones was screened for human cytochrome P450 1A1, 3A4 and 19 (aromatase) inhibition, and for antifungal activity against a panel of pathogenic fungi. The defensive role of these natural plant flavonoids as antifungal phytoalexins and phytoanticipins is discussed. [Copyright &y& Elsevier]

Abstract: Two total syntheses of fully functionalized seco-analogs of the anticancer compound pancratistatin are reported. Structure–activity relationship (SAR) studies identified potent and selective inhibitors of human cytochrome P450 3A4 (CYP3A4) and revealed several core pharmacophoric elements. These studies identify potential roadblocks and will guide the further development of a viable selective clinical pancratistatin derivative. [Copyright &y& Elsevier]

Abstract: The monodentate ligand 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phospha-adamantane (PA-Ph) is shown to be highly effective in palladium-catalyzed carbonylative cross-coupling. Aryl and vinyl halides were efficiently converted to carboxylic acids, amides and to primary, secondary, and tertiary esters, respectively. Application of the Pd(OAc)2/PA-Ph (1:1) catalyst system proved critical in the methoxycarbonylation of a functionalized nitroresorcinol halide, allowing convenient access to novel platensimycin sulfonamide analogs. [Copyright &y& Elsevier]

Abstract: A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and the natural compound narciclasine exhibited low micromolar activities. Important pharmacological features uncovered include the lack of CYP3A4 inhibitory activity seen for galanthamine and the selective activity that is seen with narciclasine over pancratistatin. [Copyright &y& Elsevier]

Abstract: The use of the ligand bis(di-tert-butylphosphino)-o-xylene (dtbpx) in palladium-catalysed carbonylative and Suzuki–Miyaura cross-coupling reactions is described. Aryl and vinyl halides readily entered into the carbonylative catalytic cycle affording carboxylic acids, amides as well as primary, secondary and tertiary esters, respectively, in good yields. Aryl iodides, bromides and chlorides gave high yields of biphenyl products upon reaction with both activated and unactivated boronic acids. [Copyright &y& Elsevier]

Abstract: The direct chemoselective differential functionalization of the ring-C hydroxyl groups present in the Amaryllidaceae alkaloid lycorine is described allowing for selective manipulation of the 1,2-hydroxyl groups. A mini-library comprised of synthetic and natural lycorane alkaloids was prepared and their apoptosis-inducing activity investigated in human leukemia (Jurkat) cells. Further insights into the nature of this interesting apoptosis-inducing pharmacophore are described, including the requirement of both free hydroxyl groups in ring-C. [Copyright &y& Elsevier]

Application of phosphonium salt ionic liquids in the carbonylation of aryl and vinyl halides is presented. Anionic effects were uncovered with the bromide ionic liquid emerging as the superior media. Acid bromide intermediates were detected in control experiments providing an extended view on the overall catalytic cycle involved. Solvent-free product isolation and recycling of the ionic liquid containing active Pd-catalyst are also demonstrated. [ABSTRACT FROM AUTHOR]

Abstract: The selective apoptosis-inducing activity of Amaryllidaceae alkaloids belonging to the crinane-type is reported. A mini-library of natural and synthetic crinane alkaloids was assembled. Biological screening indicated crinamine 4 and haemanthamine 9 to be potent inducers of apoptosis in tumour cells at micromolar concentrations. Structure-activity relationships demonstrated the requirement for both an alpha-C2 bridge and a free hydroxyl at the C-11 position as pharmacophoric requirements for this activity. [Copyright &y& Elsevier]

Automated Guided Vehicles (AGVs) are among various advanced material handling techniques that are finding increasing applications today. They can be interfaced to various other production and storage equipment and controlled through an intelligent computer control system. Both the scheduling of operations on machine centers as well as the scheduling of AGVs are essential factors contributing to the efficiency of the overall flexible manufacturing system (FMS). An increase in the performance of the FMS under consideration would be expected as a result of making the scheduling of AGVs an integral part of the overall scheduling activity. In this paper, simultaneous scheduling of parts and AGVs is done for a particular type of FMS environment by using a non-traditional optimization technique called the adaptive genetic algorithm (AGA). The problem considered here is a large variety problem (16 machines and 43 parts) and combined objective function (minimizing penalty cost and minimizing machine idle time). If the parts and AGVs are properly scheduled, then the idle time of the machining center can be minimized; as such, their utilization can be maximized. Minimizing the penalty cost for not meeting the delivery date is also considered in this work. Two contradictory objectives are to be achieved simultaneously by scheduling parts and AGVs using the adaptive genetic algorithm. The results are compared to those obtained by conventional genetic algorithm. [ABSTRACT FROM AUTHOR]

Abstract: The [Rh(acac)(CO)(L)] (acac=acetylacetonato; L1 =1,3-bis-(2,6-diisopropylphenyl)imidazolinylidene and L2 =1,3-bis-(2,4,6-trimethylphenyl)imidazolinylidene) complexes were prepared by the action of the parent carbene on [Rh(acac)(CO)2] in THF. The crystal structure characterisation of [Rh(acac)(CO)(L1)] revealed a slightly distorted square planar geometry with the carbene ligand orientated almost perpendicular to the equatorial plane; an elongated trans Rh–O bond of 2.0806(18)Å reflecting the considerable trans-influence of the carbene ligand. By measuring the CO stretching frequencies in a range of [Rh(acac)(CO)(L)] complexes (L=CO, L1, L2, PPh3, P n Bu3, P(O–2,4- t Bu2–Ph)3) the following electron donating ability series was established: L1 ∼L2 ∼P n Bu3 >PPh3 >P(O–2,4- t Bu2–Ph)3 >CO; indicating the carbenes investigated in this study to have a similar electronic cis-influence as trialkyl phosphines. Both complexes do not display hydroformylation activity towards 1-hexene in the absence of added phosphine or phosphite ligands under the conditions investigated (P=60; T =85°C). In the presence of a phosphine or phosphite ligand the resulting hydroformylation catalysis was identical to that observed for [Rh(acac)(CO)2] and the corresponding ligand and subsequent high-pressure 31P NMR studies confirmed substitution of the carbene ligand under these conditions. [Copyright &y& Elsevier]

The increased use of flexible manufacturing systems (FMS) to efficiently provide customers with diversified products has created a significant set of operational challenges. Although extensive research has been conducted on design and operational problems of automated manufacturing systems, many problems remain unsolved. In particular, the scheduling task, the control problem during the operation, is of importance owing to the dynamic nature of the FMS such as flexible parts, tools and automated guided vehicle (AGV) routings. The FMS scheduling problem has been tackled by various traditional optimisation techniques. While these methods can give an optimal solution to small-scale problems, they are often inefficient when applied to larger-scale problems. In this work, different scheduling mechanisms are designed to generate optimum scheduling; these include non-traditional approaches such as genetic algorithm (GA), simulated annealing (SA) algorithm, memetic algorithm (MA) and particle swarm algorithm (PSA) by considering multiple objectives, i.e., minimising the idle time of the machine and minimising the total penalty cost for not meeting the deadline concurrently. The memetic algorithm presented here is essentially a genetic algorithm with an element of simulated annealing. The results of the different optimisation algorithms (memetic algorithm, genetic algorithm, simulated annealing, and particle swarm algorithm) are compared and conclusions are presented . [ABSTRACT FROM AUTHOR]

Abstract: The novel compounds N-demethylbelladine, 6α-methoxybuphanidrine and filifoline, in addition to five known alkaloids, and phenol have been isolated from fresh bulbs of Nerine filifolia (Amaryllidaceae). The structure and stereochemistry of the compounds were determined by physical and spectroscopic methods, including 1D and 2D NMR and mass spectroscopic techniques. An unusual circular dichroism response from filifoline has required a semi-synthetic derivatisation strategy towards key C-11endo analogues of the β-crinane representative ambelline in which the nature of substituents was observed to have a profound effect on molecular ellipticity. Filifoline was not cytotoxic to myoblast (L6) cells and exhibited no anti-protozoal activity in an in vitro screen against four different parasitic protozoa. [Copyright &y& Elsevier]

Differential Galois theory, the theory of strongly normal extensions, has unfortunately languished. This may be due to its reliance on Kolchin's elegant, but not widely adopted, axiomatization of the theory of algebraic groups. This paper attempts to revive the theory using a differential scheme in place of those axioms. We also avoid using a universal differential field, instead relying on a certain tensor product. We identify automorphisms of a strongly normal extension with maximal differential ideals of this tensor product, thus identifying the Galois group with the closed points of an affine differential scheme. Moreover, the tensor product has a natural coring structure which translates into the Galois group operation: composition of automorphisms. This affine differential scheme splits, i.e. is obtained by base extension from a (not differential, not necessarily affine) group scheme. As a consequence, the Galois group is canonically isomorphic to the closed, or rational, points of a group scheme defined over constants. We obtain the fundamental theorem of differential Galois theory, giving a bijective correspondence between subgroup schemes and intermediate differential fields. On the way to this result we study certain aspects of differential algebraic geometry, e.g. closed immersions, products, local ringed space of constants, and split differential schemes. [ABSTRACT FROM AUTHOR]

It is well-known that the ring Γ(X,OX) of global sections of X=diffspec R is not necessarily isomorphic to R, in contrast to the situation for spec. In this paper we examine three reasons for this phenomenon: differential zeros, differential units, and the non-principality of a certain Gabriel topology. We give examples and make connections with the work of Keigher and Buium. [Copyright &y& Elsevier]

Protozoan-borne diseases are prominent amongst diseases caused by parasites. Given their alarming morbidity and mortality statistics, there is ever growing interest in new therapies against these diseases. Whilst synthetic drugs such as benznidazole and melarsoprol have had a profound influence on the clinical setup, there has been significant interest in the phytochemical platform to also deliver such drug candidates. The plant family Amaryllidaceae is recognizable for its isoquinoline alkaloids, which exhibit attractive molecular architectures and interesting biological properties. This survey focuses on the antiprotozoal activities of 73 of such substances described in 18 different species of the Amaryllidaceae. Of these, 2- O -acetyllycorine was identified as the most potent (IC 50 0.15 μg/mL against Trypansoma brucei brucei). Also considered are structure-activity relationships which have served to modulate activities, as well as the plausible mechanisms that underpin these effects and afford insight to the Amaryllidaceae alkaloid antiprotozoal pharmacophore. [ABSTRACT FROM AUTHOR]