Speeding up Monte Carlo molecular simulation by a non-conservative early rejection scheme

Monte Carlo (MC) molecular simulation describes fluid systems with rich information, and it is capable of predicting many fluid properties of engineering interest. In general, it is more accurate and representative than equations of state. On the other hand, it requires much more computational effort and simulation time. For that purpose, several techniques have been developed in order to speed up MC molecular simulations while preserving their precision. In particular, early rejection schemes are capable of reducing computational cost by reaching the rejection decision for the undesired MC trials at an earlier stage in comparison to the conventional scheme. In a recent work, we have introduced a ‘conservative’ early rejection scheme as a method to accelerate MC simulations while producing exactly the same results as the conventional algorithm. In this paper, we introduce a ‘non-conservative’ early rejection scheme, which is much faster than the conservative scheme, yet it preserves the precision of the method. The proposed scheme is tested for systems of structureless Lennard-Jones particles in both canonical and NVT-Gibbs ensembles. Numerical experiments were conducted at several thermodynamic conditions for different number of particles. Results show that at certain thermodynamic conditions, the non-conservative method is capable of doubling the speed of the MC molecular simulations in both canonical and NVT-Gibbs ensembles.     

Physiological mechanisms of regulating alloimmunity: cytokines,CTLA-4, CD25+ cells,and the alloreactive T cell clone size

The mechanisms underlying physiological regulation of alloimmune responses remain poorly defined. We investigated the roles of cytokines, CTLA-4, CD25(+) T cells, and apoptosis in regulating alloimmune responses in vivo. Two murine cardiac transplant models were used, B10.D2 (minor mismatch) and C57BL/6 (major mismatch), into BALB/c recipients. Recipients were wild type, STAT4(-/-) (Th1 deficient), or STAT6(-/-) (Th2 deficient) mice. Minor mismatched allografts were accepted spontaneously in approximately 70% of wild type and STAT4(-/-) mice. By contrast, there was significantly shorter graft survival in minor mismatched STAT6(-/-) mice. Either the adoptive transfer of STAT4(-/-) splenocytes or the administration of IL-4Fc fusion protein into STAT6(-/-) mice resulted in long term graft survival. Blocking CTLA-4 signaling accelerated the rejection in all recipients, but was more pronounced in the minor combination. This was accompanied by an increased frequency of alloreactive T cells. Furthermore, CTLA-4 blockade regulated CD4(+) or CD8(+) as well as Th1 or Th2 alloreactive T cells. Finally, while anti-CD25 treatment prolonged graft survival in the major mismatched combination, the same treatment accelerated graft rejection in the minor mismatched group. The latter was associated with an increased frequency of alloreactive T cells and inhibition of T cell apoptosis. These data demonstrate that cytokine regulation, CTLA-4 negative signaling, and T cell apoptosis play critical roles in regulating alloimmunity, especially under conditions where the alloreactive T cell clone size is relatively small.     

Piericidin A Aggravates Tau Pathology in P301S Transgenic Mice

ObjectiveThe P301S mutation in exon 10 of the tau gene causes a hereditary tauopathy. While mitochondrial complex I inhibition has been linked to sporadic tauopathies. Piericidin A is a prototypical member of the group of the piericidins, a class of biologically active natural complex I inhibitors, isolated from streptomyces spp. with global distribution in marine and agricultural habitats. The aim of this study was to determine whether there is a pathogenic interaction of the environmental toxin piericidin A and the P301S mutation.MethodsTransgenic mice expressing human tau with the P301S-mutation (P301S^+/+) and wild-type mice at 12 weeks of age were treated subcutaneously with vehicle (N = 10 P301S^+/+, N = 7 wild-type) or piericidin A (N = 9 P301S^+/+, N = 9 wild-type mice) at a dose of 0.5 mg/kg/d for a period of 28 days via osmotic minipumps. Tau pathology was measured by stereological counts of cells immunoreative with antibodies against phosphorylated tau (AD2, AT8, AT180, and AT100) and corresponding Western blot analysis.ResultsPiericidin A significantly increased the number of phospho-tau immunoreactive cells in the cerebral cortex in P301S^+/+ mice, but only to a variable and mild extent in wild-type mice. Furthermore, piericidin A led to increased levels of pathologically phosphorylated tau only in P301S^+/+ mice. While we observed no apparent cell loss in the frontal cortex, the synaptic density was reduced by piericidin A treatment in P301S^+/+ mice.DiscussionThis study shows that exposure to piericidin A aggravates the course of genetically determined tau pathology, providing experimental support for the concept of gene-environment interaction in the etiology of tauopathies.     

A naphthyl analog of the aminostyryl pyridinium class of potentiometric membrane dyes shows consistent sensitivity in a variety of tissue,cell, and model membrane preparations

The fast potentiometric indicator di-4-ANEPPS is examined in four different preparations: lipid vesicles, red blood cells, squid giant axon, and guinea pig heart. The dye gives consistent potentiometric responses in each of these systems, although some of the detailed behavior varies. In lipid vesicles, the dye displays an increase in fluorescence combined with a red shift of the excitation spectrum upon hyperpolarization. Similar behavior is found in red cells where a dual wavelength radiometric measurement is also demonstrated. The signal-to-noise ratio of the potentiometric fluorescence response is among the best ever recorded on the voltage-clamped squid axon. The dye is shown to be a faithful and persistent monitor of cardiac action potentials with no appreciable loss of signal or deterioration of cardiac activity for periods as long as 2 hr with intermittent illumination every 10 min. These results, together with previously published applications of the dye to a spherical lipid bilayer model and to cells in culture, demonstrate the versatility of di-4-ANEPPS as a fast indicator of membrane potential.     

Prion protein does not redox-silence Cu2+, but is a sacrificial quencher of hydroxyl radicals

Oxidative stress is believed to play a central role in the pathogenesis of prion diseases, a group of fatal neurodegenerative disorders associated with a conformational change in the prion protein (PrP(C)). The precise physiological function of PrP(C) remains uncertain; however, Cu(2+) binds to PrP(C) in vivo, suggesting a role for PrP(C) in copper homeostasis. Here we examine the oxidative processes associated with PrP(C) and Cu(2+). (1)H NMR was used to monitor chemical modifications of PrP fragments. Incubation of PrP fragments with ascorbate and CuCl(2) showed specific metal-catalyzed oxidation of histidine residues, His(96/111), and the methionine residues, Met(109/112). The octarepeat region protects His(96/111) and Met(109/112) from oxidation, suggesting that PrP(90-231) might be more prone to chemical modification. We show that Cu(2+/+) redox cycling is not 'silenced' by Cu(2+) binding to PrP, as indicated by H(2)O(2) production for full-length PrP. Surprisingly, although detection of Cu(+) indicates that the octarepeat region of PrP is capable of reducing Cu(2+) even in the absence of ascorbate, H(2)O(2) is not generated unless ascorbate is present. Full-length PrP and fragments cause a dramatic reduction in detectable hydroxyl radicals in an ascorbate/Cu(2+)/O(2) system; however, levels of H(2)O(2) production are unaffected. This suggests that PrP does not affect levels of hydroxyl radical production via Fentons cycling, but the radicals cause highly localized chemical modification of PrP(C).     

蒜香藤叶挥发油的化学成分

蒜香藤（Pseudocalymma alliaceum Sandw．）又名紫铃藤,为紫葳科（Bignoniaceae）常绿藤状灌木,原产于南美洲的圭亚那和巴西。蒜香藤花、叶在搓揉之后,有浓浓的大蒜香味,其叶深绿富有光泽,花形大而优美,中国许多地方已引种栽培,一般作为篱笆、围墙美化或凉亭、棚架装饰之用。蒜香藤具有浓郁的蒜香,甚至可作为蒜的替代物用于烹饪。但有关其叶挥发性成分研究尚未见报道。本文利用气相色谱-质谱联用技术（GC—MS）分析了西双版纳植物园引种栽培的蒜香藤叶挥发油的化学成分,以期为合理开发和利用蒜香藤植物资源提供科学依据。     

Effect of ultraviolet radiation on chlorophyll,carotenoid, protein and proline contents of some annual desert plants

Investigation was carried out to find whether enhanced ultraviolet radiation influences the Malva parviflora L., Plantago major L., Rumex vesicarius L. and Sismbrium erysimoids Desf. of some annual desert plants. The seeds were grown in plastic pots equally filled with a pre-sieved normal sandy soil for 1 month. The planted pots from each species were randomly divided into equal groups (three groups). Plants of the first group exposed to white-light tubes (400–700 nm) 60 w and UV (365 nm) 8 w tubes. The second group was exposed to white-light tubes (400–700 nm) 60 w and UV (302 nm) 8 w tubes. The third group was exposed to white-light tubes (400–700 nm) 60 w and UV (254 nm) 8 w tubes, respectively, for six days. The results indicated that the chlorophyll contents were affected by enhanced UV radiation. The chlorophyll a, b, and total contents were decreased compared with the control values and reduced with the enhanced UV radiation, but the carotenoid was increased compared with the control and also reduced with the enhanced UV radiation. So, the contents of chlorophylls varied considerably. M. parviflora showed the highest constitutive levels of accumulated chlorophyll a, b, and total chlorophyll (0.463, 0.307 and 0.774 mg g⁻¹ f w) among the investigated plant species. P. major showed the lowest constitutive levels of the chloroplast pigments, 0.0036, 0.0038 and 0.0075 mg g⁻¹ f w for chlorophyll a, b, and total chlorophyll at UV-365 nm, respectively. The protein content was decreased significantly in both root and shoot systems compared with the control values but, it was increased with increasing wave lengths of UV-radiation of all tested plants. R. vesicarius showed the highest protein contents among the investigated plants; its content was 3.8 mg g⁻¹ f w at UV-365 nm in shoot system. On the other hand, decreasing ultraviolet wave length induced a highly significant increase in the level of proline in both root and shoot of all tested plants. From the results obtained, it is suggested that proline can protect cells against damage induced by ultraviolet radiation. Statistically, the variations of the studied metabolic activities were significant due to UV radiation treatment in shoot and root system of all investigated plant species.     

Production of DON-related trichothecenes byFusarium graminearum Schw from Krasnodarski krai of the USSR

34Fusarium graminearum Schw isolates produced 4-deoxynivalenol to form significant amounts of 4, 7 — dideoxynivalenol and lesser amounts of 4 — deoxynivalenol monoacetates on grain substratesin vitro. This is the first report on the capability a large group of naturally occurring isolates to produce 4,7-dideoxynivalenol. The average levels of 4,7-dideoxynivalenol on rice, corn, barley, and wheat as a substrate were respectively 26.8, 14.0, 12.8, and 10.5% of the level of 4-deoxynivalenol. 4, 7 — dideoxynivalenol was present in all examined naturally contaminated wheat kernel samples at levels of 1.7 to 7.9% of the level of 4-deoxynivalenol. These findings suggest that more attention should be given to the occurrence of 4,7-dideoxynivalenol in cereals.     

Anti-Ulcerogenic Effect of Methanolic Extracts from Enicosanthellum pulchrum (King) Heusden against Ethanol-Induced Acute Gastric Lesion in Animal Models

A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2–7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4–7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol.     

Selenium nanoparticles from Lactobacillus paracasei HM1 capable of antagonizing animal pathogenic fungi as a new source from human breast milk

The current study was performed to develop a simple, safe, and cost-effective technique for the biosynthesis of selenium nanoparticles (SeNPs) from lactic acid bacteria (LAB) isolated from human breast milk with antifungal activity against animal pathogenic fungi. The LAB was selected based on their speed of transforming sodium selenite (Na₂SeO₃) to SeNPs. Out of the four identified LAB isolates, only one strain produced dark red color within 32 h of incubation, indicating that this isolate was the fastest in transforming Na₂SeO₃ to SeNPs; and was chosen for the biosynthesis of LAB-SeNPs. The superior isolate was further identified as Lactobacillus paracasei HM1 (MW390875) based on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and phylogenetic tree analysis of 16S rRNA sequence alignments. The optimum experimental conditions for the biosynthesis of SeNPs by L. paracasei HM1 were found to be pH (6.0), temperature (35˚C), Na₂SeO₃ (4.0 mM), reaction time (32 h), and agitation speed (160 rpm). The ultraviolet absorbance of L. paracasei-SeNPs was detected at 300 nm, and the transmission electron microscopy (TEM) captured a diameter range between 3.0 and 50.0 nm. The energy-dispersive X-ray spectroscopy (EDX) and the Fourier-transform infrared spectroscopy (FTIR) provided a clear image of the active groups associated with the stability of L. paracasei-SeNPs. The size of L. paracasei-SeNPs using dynamic light scattering technique was 56.91 ± 1.8 nm, and zeta potential value was −20.1 ± 0.6 mV in one peak. The data also revealed that L. paracasei-SeNPs effectively inhibited the growth of Candida and Fusarium species, and this was further confirmed by scanning electron microscopy (SEM). The current study concluded that the SeNPs obtained from L. paracasei HM1 could be used to prepare biological antifungal formulations effective against major animal pathogenic fungi. The antifungal activity of the biologically synthesized SeNPs using L. paracasei HM1 outperforms the chemically produced SeNPs. In vivo studies showing the antagonistic effect of SeNPs on pathogenic fungi are underway to demonstrate the potential of a therapeutic agent to treat animals against major infectious fungal diseases.