Neuromuscular control of the point to point and oscillatory movements of a sagittal arm with the actor–critic reinforcement learning method

In this study, we have used a single link system with a pair of muscles that are excited with alpha and gamma signals to achieve both point to point and oscillatory movements with variable amplitude and frequency.

The system is highly nonlinear in all its physical and physiological attributes. The major physiological characteristics of this system are simultaneous activation of a pair of nonlinear muscle-like-actuators for control purposes, existence of nonlinear spindle-like sensors and Golgi tendon organ-like sensor, actions of gravity and external loading. Transmission delays are included in the afferent and efferent neural paths to account for a more accurate representation of the reflex loops.

A reinforcement learning method with an actor–critic (AC) architecture instead of middle and low level of central nervous system (CNS), is used to track a desired trajectory. The actor in this structure is a two layer feedforward neural network and the critic is a model of the cerebellum. The critic is trained by state-action-reward-state-action (SARSA) method. The critic will train the actor by supervisory learning based on the prior experiences. Simulation studies of oscillatory movements based on the proposed algorithm demonstrate excellent tracking capability and after 280 epochs the RMS error for position and velocity profiles were 0.02, 0.04?rad and rad/s, respectively.     

Effects of point mutations in pVHL on the binding of HIF-1α

The von Hippel-Lindau tumor suppressor protein (pVHL) has an essential role in the regulation of the hypoxia response pathway in animal cells. Under normoxic conditions, the hypoxia-inducible factor (HIF) undergoes trans-4-prolyl hydroxylation and is subsequently recognised by the β-domain of pVHL, leading to the ubiquitination and degradation of HIF. Mutations of pVHL alter the binding of HIF. A subset of relevant clinically observed mutations to pVHL are thought to cause weaker binding of HIF-1α and are associated with cancer and cardiovascular diseases. Here, we present computational studies analyzing the interaction of HIF with mutant forms of pVHL, describing at atomic detail the local structural reorganization caused by substitution of certain residues of pVHL. The results reveal that the canonical configuration in the wild-type system is vital for the efficient functioning of the complex and that mutation of any of the residues implicated in the h-bond network in the binding site disrupts HIF binding. Although the experimentally observed ordering of binding energies for mutants of Tyr98 is reproduced, our examination of a broader range of mutations does not support the hypothesis of a correlation between the degree of disruption of the pVHL/HIF-1α interaction caused by a mutation and the phenotype with which the mutation is associated. We suggest that disruption of the binding interaction is one of many factors behind the manifestation of VHL disease.     

Evidence of a tipping point in a southern African savanna?

Many ecosystems exhibit threshold behaviour, where periods of relative stability are punctuated by rapid transitions between alternate stable states when an ecological threshold, or tipping point, is reached. This is of concern in grass-dominated habitats, many of which appear to be on the point of conversion to more wooded vegetation assemblages. However, changes in grass-dominated ecosystems are often difficult to interpret, because it is not always clear whether grasslands are ancient or are anthropogenically derived from past deforestation. As a result, the conservation, maintenance and restoration of ancient grasslands are sometimes neglected.In this study, the history of vegetation change in the savannas of the Hluhluwe-iMfolozi Park, KwaZulu-Natal, South Africa, are investigated by analysing stable carbon isotopes (δ¹³C) from soil profiles. Without exception, the data show that C₃ dominated thicket, forest, and densely wooded savanna now occur on sites that were previously C₄ grassland or open savanna. Although the drivers of this change are not clear, there is potential for management intervention because tree density can be manipulated through fire, a natural part of this dynamic landscape. The study identified two sites which are at a threshold between C₄ and C₃ dominance, and highlighted them as priorities for conservation management intervention.     

How specific are "target-specific" drugs? Celecoxib as a case in point

With the push to develop the next blockbuster drugs, continued surveillance of current bestsellers may not be given the full attention due. Upon wide-spread use, unexpected adverse effects begin to emerge. Although touted as highly specific, many of the newly developed drugs are likely to have secondary molecular targets-a potential cause of adverse effects. A molecular pharmacology approach that screens for multiple drug targets may shed light on the mechanisms that underlie both desired and adverse side-effects.     

Structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations

Protein tyrosine phosphatase ρ (PTPρ) belongs to the classical receptor type IIB family of protein tyrosine phosphatase, the most frequently mutated tyrosine phosphatase in human cancer. There are evidences to suggest that PTPρ may act as a tumor suppressor gene and dysregulation of Tyr phosphorylation can be observed in diverse diseases, such as diabetes, immune deficiencies and cancer. PTPρ variants in the catalytic domain have been identified in cancer tissues. These natural variants are nonsynonymous single nucleotide polymorphisms, variations of a single nucleotide occurring in the coding region and leading to amino acid substitutions. In this study we investigated the effect of amino acid substitution on the structural stability and on the activity of the membrane-proximal catalytic domain of PTPρ. We expressed and purified as soluble recombinant proteins some of the mutants of the membrane-proximal catalytic domain of PTPρ identified in colorectal cancer and in the single nucleotide polymorphisms database. The mutants show a decreased thermal and thermodynamic stability and decreased activation energy relative to phosphatase activity, when compared to wild- type. All the variants show three-state equilibrium unfolding transitions similar to that of the wild- type, with the accumulation of a folding intermediate populated at ~4.0 M urea.     

Patterns of phylogenetic relatedness of non-native plants across the introduction-naturalization-invasion continuum in ChinaOA

Human activities have caused the exchange of species among different parts of the world.When introduced species become naturalized and invasive,they may cause great negative impacts on the environment and human societies,and pose significant threats to biodiversity and ecosystem structure.Knowledge on phylogenetic relatedness between native and non-native species and among non-native species at different stages of species invasion may help for better understanding the drivers of species invasion...     

Geographic patterns of taxonomic and phylogenetic β-diversity of aquatic angiosperms in ChinaOA

China covers a vast territory harbouring a large number of aquatic plants.Although there are many studies on the β-diversity of total,herbaceous or woody plants in China and elsewhere,few studies have focused on aquatic plants.Here,we analyse a comprehensive data set of 889 aquatic angiosperm species in China,and explore the geographic patterns and climatic correlates of total taxonomic and phylogeneticβ-diversity as well as their turnover and nestedness components.Our results show that geograph...     

The synthesis of the α-d-anomers of “homonucleosides”: derivatives of 2,5-anhydro-d-altritol

Reaction of 2,3,5-tri-O-benzyl-d-ribofuranosyl bromide with mercuric cyanide afforded an anomeric mixture of cyanides (3) and 1,4-anhydro-2,3,5-tri-O-benzyl-d-erythro-pent-1-enitol (6). Reduction of 3 with lithium aluminum hydride gave a pair of epimeric amines (4 and 5), which were separated by chromatography and characterized by conversion into the known 2,5-anhydro-3,4,6-tri-O-benzyl-1-deoxy-1-ureido-d-allitol (7) and its epimer, 2,5-anhydro-3,4,6-tri-O-benzyl-1-deoxy-1-ureido-d-altritol (8). Compound 8 and its precursor were used for the synthesis of various “α-homonucleosides”.     

Derivatives of β-D-fructofuranosyl α-D-galactopyranoside

De-etherification of 6,6′-di-O-tritylsucrose hexa-acetate (2) with boiling, aqueous acetic acid caused 4→6 acetyl migration and gave a syrupy hexa-acetate 14, characterised as the 4,6′-dimethanesulphonate 15. Reaction of 2,3,3′4′,6-penta-O-acetylsucrose (5) with trityl chloride in pyridine gave a mixture containing the 1′,6′-diether 6 the 6′-ether 9, confirming the lower reactivity of HO-1′ to tritylation. Subsequent mesylation, detritylation, acetylation afforded the corresponding 4-methanesulphonate 8 1′,4-dimethanesulphonate 11. Reaction of these sulphonates with benzoate, azide, bromide, and chloride anions afforded derivatives of β-D-fructofuranosyl α-D-galactopyranoside (29) by inversion of configuration at C-4. Treatment of the 4,6′-diol 14 the 1,′4,6′-triol 5, the 4-hydroxy 1′,6′-diether 6 with sulphuryl chloride effected replacement of the free hydroxyl groups and gave the corresponding, crystalline chlorodeoxy derivatives. The same 4-chloro-4-deoxy derivative was isolated when the 4-hydroxy-1′,6′-diether 6 was treated with mesyl chloride in N,N-dimethylformamide.     

Insights into cryptic speciation of quillworts in ChinaOA

Cryptic species are commonly misidentified because of high morphological similarities to other species.One group of plants that may harbor large numbers of cryptic species is the quillworts(Iso?tes spp.),an ancient aquatic plant lineage.Although over 350 species of Iso?tes have been reported globally,only ten species have been recorded in China.The aim of this study is to better understand Iso?tes species diversity in China.For this purpose,we systematically explored the phylogeny and evolution ...     

Fungal culture of musculoskeletal tissue: what’s the point?

There have not been any studies that review the prevalence of fungal isolates using selective media from samples of banked musculoskeletal tissue retrieved from living and cadaveric donors. A total of 2,036 swab and 2,621 biopsy samples of musculoskeletal tissue from tissue banks were received from the 1st August 2008 till 31st December 2010. Routine culture for fungi using selective media with a prolonged incubation period failed to demonstrate a greater prevalence of fungal isolates than by using non-selective culture media alone. Using selective culture fungi were recovered from only two Sabouraud agar plates (0.1%) but not from non-selective media. During the same period fungi were isolated from three graft samples cultured in non-selective broth media only (0.1%). There was no correlation of fungal isolates from selective or non-selective media inoculated at the same time nor from multiple graft samples collected from the same donor supporting the possibility of an exogenous source for fungal isolates rather than an endogenous source.     

Oil pollution in the North Sea—a microbiological point of view

In this study we determined oil degradation rates in the North Sea under most natural conditions. We used the heavy fuel oil, Bunker C, the major oil pollutant of the North Sea, as the model oil. Experiments were conducted in closed systems with water sampled during winter and repeated under identical conditions with water collected during summer. No nitrogen or phosphorous was added and conditions were chosen such that neither oxygen nor nutrients, present in the water, would become limiting during the experiments. We detected a fourfold increased degradation rate for water samples taken in summer (18°C water temperature) as compared to water sampled in winter (4°C water temperature). Under the assumption that biodegradation of oil can be regarded as a Michaelis-Menten type kinetic reaction, the kinectic constants V_max and K_M were determined for oil biodegradation at 4°C and 18°C. At both temperatures K_M was about 40 ppm, whereas V_max was 3–4 times higher at 18°C. From both V_max and the results of fermentation studies, we determined the maximum rates of Bunker C oil degradation in the North Sea as ∼20 g m⁻³a⁻¹ at 4°C in winter and 60–80 g m⁻³a⁻¹ at 18°C in summer. Furthermore, while over 25% of the oil was degraded within 6 weeks in summer, only 6.6% of the oil was degraded in winter. A higher incubation temperature in winter (18°C) increased both the rate and the percentage of oil degraded, but degradation did not reach the level obtained during the summer. While these data reflect the oxidation only of the hydrocarbons, we conducted experiments directly in the open sea to determine the contribution of abiotic factors to oil removal. Approximately 42% of the oil was lost within 6 weeks under these conditions in summer and 65% in winter. However, GC-MS analysis of the recovered oil showed no significant change in the alkane pattern that would indicate enhanced degradation. Thus, mainly abiotic factors such as erosion and dispersion rather than degradation were responsible for enhanced oil removal. Especially the high loss during winter can be attributed to frequent storms resulting in greater dispersion. In conclusion, the higher oil degrading potential of the microbial population in the North Sea was represented by a four times faster oil degradation during the summer. In-situ experiments showed that abiotic factors can have an equal (summer) or even higher (winter) impact on oil removal.     

Monomolar acetalations of methyl α-d-mannosides—synthesis of methyl α-d-talopyranoside

Methyl α-d-mannopyranoside (1 mole) reacts with 2,2-dimethoxypropane (1 mole), to give the 4,6-O-isopropylidene derivative (2) which rearranges to the 2,3-O-isopropylidene derivative (4). Compound4 can also be prepared by graded hydrolysis of methyl 2,3:4,6-di-O-isopropylidene-α-d-mannopyranoside. Successive benzoylation, oxidation, and reduction of4 provides a useful route to a number ofd-talopyranoside compounds. Methyl α-d-mannofuranoside (1 mole) reacts with 1–2 moles of 2,2-dimethoxypropane to give the 5,6-O-isopropylidene derivative (16) in 90% yield.     

Distribution and conservation of near threatened plants in ChinaOA

Plants classified as Near Threatened(NT) are at high risk of becoming threatened because of anthropogenic interference and climate change.Especially in conservation efforts,such species have however long been overlooked.Here,we obtained 98,419 precise occurrence points for 2442 NT plants in China,and used species richness,species complementarity,and weighted endemism that consider all,endemic and narrow-ranged species in order to identify the diversity hotspots of NT plants.Then we evaluated the...     

Global patterns of taxonomic and phylogenetic diversity of flowering plants:Biodiversity hotspots and coldspotsOA

Species diversity of angiosperms(flowering plants) varies greatly among regions.Geographic patterns of variation in species diversity are shaped by the interplay of ecological and evolutionary processes.Here,using a comprehensive data set for regional angiosperm floras across the world,we show geographic patterns of taxonomic(species) diversity,phylogenetic diversity,phylogenetic dispersion,and phylogenetic deviation(i.e.,phylogenetic diversity after accounting for taxonomic diversity) across th...     

Antibacterial activity and mechanism of action of ε-poly-l-lysine

ε-Poly-l-lysine (ε-PL)² is widely used as an antibacterial agent because of its broad antimicrobial spectrum. However, the mechanism of ε-PL against pathogens at the molecular level has not been elucidated. This study investigated the antibacterial activity and mechanism of ε-PL against Escherichia coli O157:H7 CMCC44828. Propidium monoazide-PCR test results indicated that the threshold condition of ε-PL for complete membrane lysis of E. coli O157:H7 was 10 μg/mL (90% mortality for 5 μg/mL). Further verification of the destructive effect of ε-PL on cell structure was performed by atomic force microscopy and transmission electron microscopy. Results showed a positive correlation between reactive oxygen species (ROS) ³ levels and ε-PL concentration in E. coli O157:H7 cells. Moreover, the mortality of E. coli O157:H7 was reduced when antioxidant N-acetylcysteine was added. Results from real-time quantitative PCR (RT-qPCR) ⁴ indicated that the expression levels of oxidative stress genes sodA and oxyR were up-regulated 4- and 16-fold, respectively, whereas virulence genes eaeA and espA were down-regulated after ε-PL treatment. Expression of DNA damage response (SOS response) ⁵ regulon genes recA and lexA were also affected by ε-PL. In conclusion, the antibacterial mechanism of ε-PL against E. coli O157:H7 may be attributed to disturbance on membrane integrity, oxidative stress by ROS, and effects on various gene expressions, such as regulation of oxidative stress, SOS response, and changes in virulence.     

Synthesis of 5-O-β-D-galactofuranosyl-D-galactofuranose

Conversion of benzyl αβ-D-galactofuranoside into the 5,6-O-[α-(dimethyl-amino)benzylidene] derivative, followed by acetylation of HO-2 and HO-3, and selective ring opening or the acetal, gave benzyl 2,3-di-O-acetyl-6-O-benzoyl-αβ-D-galactofuranoside(4). The title disaccharide was synthesised from4 by reaction with 3,4,6-tri-O-acetyl-α-D-galactofuranose 1,2-(methyl orthoacetate) followed by removal of protecting groups     

Synthesis of 4-O-β-D-mannopyranosyl-L-rhamnopyranose

The title disaccharide (16) has been synthesized in 50% overall yield by way of condensation of 4,6-di-O-acetyl-2,3-O-carbonyl-α-D-mannopyranosyl bromide 5 with methyl 2,3-O-isopropylidene-α-L-rhamnopyranoside (1) in chloroform solution, in the presence of silver oxide. The disaccharide was characterized as the crystalline isopropyl alcoholate of methyl 4-O-β-D-mannopyranosyl-α-L-rhamnopyranoside (11) and as 1,2,3-tri-O acetyl-4-O- (2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl)-α-L-rhamnopyranose (15). Methyl β-D-mannopyranoside isopropyl alcoholate 7 was readily obtained in 85% yield via the reaction of bromide 5 with methanol.Reduction of 2,3-di-O-methyl-L-rhamnose with sodium borohydride, followed by acetylation, may result in the formation of an appreciable proportion of a boric ester, namely 1,5-di-O-acetyl-4-deoxy-2,3-di-O-methyl-L-rhamnitol-4-yl dimethyl borate, depending on the procedure used.