Post-polymerization functionalization of poly(ethylene oxide)–poly(β-6-heptenolactone) diblock copolymers to tune properties and self-assembly

Copolymers were synthesized and functionalized with a variety of moieties to tune self-assembly and install drugs or fluorescent dyes. , Polyester-based amphiphilic block copolymers and their nanoassemblies are of significant interest for a wide range of applications due to the degradability of the polyester block. However, the commonly used polyesters lack functional groups on their backbones, limiting the possibilities to chemically modify these polymers. Described here are new poly(ethylene oxide) (PEO)–poly(β-6-heptenolactone) (PHEL) block copolymers having pendant alkenes at each repeat unit on the PHEL block. First, the self-assembly of these block copolymers in aqueous solution was studied and it was found that they formed solid nanoparticles and vesicles depending on the relative block lengths. Next the alkene moieties of the block copolymer were modified with either hydrophilic or hydrophobic pendant groups using thiol–ene reactions, allowing the hydrophilic mass fractions and consequently the self-assembled morphologies to be tuned, accessing both smaller nanoparticles and cylindrical assemblies. It was also demonstrated that the anti-cancer drug paclitaxel or a fluorescent rhodamine dye could be easily conjugated to the block copolymers and the self-assembly of these conjugates was explored. Overall, the results of this study demonstrate that PEO-PHEL block copolymers can serve as versatile backbones for the preparation of functional, polyester-based materials

Double-Peaked Broad Emission Lines in NGC 4450 and Other LINERs

Spectra taken with HST reveal that NGC 4450 emits Balmer emission lines with displaced double peaks and extremely high-velocity wings. This characteristic line profile, previously seen in a few nearby LINERs and in a small fraction of broad-line radio galaxies, can be interpreted as a kinematic signature of a relativistic accretion disk. We can reproduce the observed profile with a model for a disk with a radial range of 1000-2000 gravitational radii and inclined by 27 degrees along the line of sight. The small-aperture HST data also allow us to detect, for the first time, the featureless continuum at optical wavelengths in NGC 4450; the nonstellar nucleus is intrinsically very faint, with M_B = -11.2 mag for D = 16.8 Mpc. We have examined the multiwavelength properties of NGC 4450 collectively with those of other low-luminosity active nuclei which possess double-peaked broad lines and find a number of common features. These objects are all classified spectroscopically as "type 1" LINERs or closely related objects. The nuclear luminosities are low, both in absolute terms and relative to the Eddington rates. All of them have compact radio cores, whose strength relative to the optical nuclear emission places them in the league of radio-loud active nuclei. The broad-band spectral energy distributions of these sources are most notable for their deficit of ultraviolet emission compared to those observed in luminous Seyfert 1 nuclei and quasars. The double-peaked broad-line radio galaxies Arp 102B and Pictor A have very similar attributes. We discuss how these characteristics can be understood in the context of advection-dominated accretion onto massive black holes.Comment: To appear in The Astrophysical Journal. Latex, 15 pages, embedded figures and tabl

Detection of foot-and-mouth disease virus in milk samples by real-time reverse transcription polymerase chain reaction: Optimisation and evaluation of a high-throughput screening method with potential for disease surveillance

This study aimed to evaluate the utility of milk as a non-invasive sample type for the surveillance of foot-and-mouth disease (FMD), a highly contagious viral disease of cloven-hooved animals. Four milking Jersey cows were infected via direct-contact with two non-milking Jersey cows that had been previously inoculated with FMD virus (FMDV: isolate O/UKG/34/2001). Milk and blood were collected throughout the course of infection to compare two high-throughput real-time reverse transcription polymerase chain reaction (rRT-PCR) protocols with different RT-PCR chemistries. Using both methods, FMDV was detected in milk by rRT-PCR one to two days before the presentation of characteristic foot lesions, similar to detection by virus isolation. Furthermore, rRT-PCR detection from milk was extended, up to 28 days post contact (dpc), compared to detection by virus isolation (up to 14 dpc). Additionally, the detection of FMDV in milk by rRT-PCR was possible for 18 days longer than detection by the same method in serum samples. FMDV was also detected with both rRT-PCR methods in milk samples collected during the UK 2007 outbreak. Dilution studies were undertaken using milk from the field and experimentally-infected animals, where for one sample it was possible to detect FMDV at 10 . Based on the peak C values detected in this study, these findings indicate that it could be possible to identify one acutely-infected milking cow in a typical-sized dairy herd (100-1000 individuals) using milk from bulk tanks or milk tankers. These results motivate further studies using milk in FMD-endemic countries for FMD surveillance

EFFECT OF A NITRIC OXIDE PRE-WORKOUT SUPPLEMENT ON MUSCULAR ENDURANCE

Introduction: Multi-ingredient dietary supplements have been developed to increase nitric oxide (NO) production, with the expectation of improving resistance training performance. Many of these supplements contain ingredients and/ or ingredient amounts that have yet to be studied for their synergy or efficacy in increasing NO production and thus, resistance training performance. Purpose of the study: A randomized crossover design was used to investigate the effect of a citrulline malate (CM) based non-stimulant nitric oxide pre-workout supplement (NOPWS) blend or placebo on Young Men’s Christian Association (YMCA) bench press performance. Applied Methodology: Thirty-minutes were provided between NOPWS or placebo ingestion and YMCA bench press assessment. Pre/post heart rate was taken following each condition. Two- and one-way repeated measures ANOVAs (α = 0.05) were run to determine the effect of each condition on heart rate (HR) and the number of repetitions performed (respectively) during the bench press test. Achieved major results: There was a significant two-way interaction between the treatment and time for HR, F(1, 20) = 6.82, p = .017. Resting HR was significantly higher during the supplement session (M = 74.67, SE = 2.54 bpm) than during the placebo session (M = 69.14, SE = 2.31 bpm), F(1, 20) = 8.19, p = .010, ηp 2 = .290. No significant difference was found between conditions for number of repetitions performed. Leads: A specific CM-containing NOPWS blend had no significant effect on a standardized assessment of upper body muscular endurance. Practical implications: These findings highlight the need for consideration of the minimum effective dosage and assimilation timing of each respective ingredient when developing or researching pre-workout supplement blends. Originality/Value: This is the first known research to study the effectiveness of this specific blend of ingredients on resistance training performance. Thus, this study provides necessary foundational knowledge for future research in this area

Low birthweight and preterm birth in young people with special educational needs: a magnetic resonance imaging analysis

<p>Abstract</p> <p>Background</p> <p>Although neuroanatomical and cognitive sequelae of low birthweight and preterm birth have been investigated, little is understood as to the likely prevalence of a history of low birthweight or preterm birth, or neuroanatomical correlates of such a history, within the special educational needs population. Our aim was to address these issues in a sample of young people receiving additional learning support.</p> <p>Methods</p> <p>One hundred and thirty-seven participants aged 13–22 years, receiving additional learning support, were recruited via their schools or colleges and underwent structural magnetic resonance imaging (MRI). Obstetric records, available in 98 cases, included birthweight and gestational data in 90 and 95 cases, respectively. Both qualitative and quantitative voxel-based analyses of MRI data were conducted.</p> <p>Results</p> <p>A history of low birthweight and preterm birth was present in 13.3% and 13.7% of cases, respectively. Low birthweight and preterm birth were associated with specific qualitative anomalies, including enlargement of subarachnoid cisterns and thinning of the corpus callosum. Low birthweight was associated with reduced grey matter density (GMD) in the superior temporal gyrus (STG) bilaterally, left inferior temporal gyrus and left insula. Prematurity of birth was associated with reduced GMD in the STG bilaterally, right inferior frontal gyrus and left cerebellar hemisphere. Comparison of subjects with no history of low birthweight or preterm birth with a previously defined control sample of cognitively unimpaired adolescents (<it>n </it>= 72) demonstrated significantly greater scores for several anomalies, including thinning of the corpus callosum, loss of white matter and abnormalities of shape of the lateral ventricles.</p> <p>Conclusion</p> <p>Although a two-fold increased prevalence of a history of low birthweight and preterm birth exists within the special educational needs population, other aetiological factors must be considered for the overwhelming majority of cases. Neuroanatomical findings within this sample include qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. These findings suggest a neurodevelopmental mechanism for the cognitive difficulties associated with these obstetric risk factors.</p

Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice

Increasing the expression of Hsp70 (heat-shock protein 70) can inhibit sensory neuron degeneration after axotomy. Since the onset of DPN (diabetic peripheral neuropathy) is associated with the gradual decline of sensory neuron function, we evaluated whether increasing Hsp70 was sufficient to improve several indices of neuronal function. Hsp90 is the master regulator of the heat-shock response and its inhibition can up-regulate Hsp70. KU-32 (N-{7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy]-8-methyl-2-oxo-2H-chromen-3-yl}acetamide) was developed as a novel, novobiocin-based, C-terminal inhibitor of Hsp90 whose ability to increase Hsp70 expression is linked to the presence of an acetamide substitution of the prenylated benzamide moiety of novobiocin. KU-32 protected against glucose-induced death of embryonic DRG (dorsal root ganglia) neurons cultured for 3 days in vitro. Similarly, KU-32 significantly decreased neuregulin 1-induced degeneration of myelinated Schwann cell DRG neuron co-cultures prepared from WT (wild-type) mice. This protection was lost if the co-cultures were prepared from Hsp70.1 and Hsp70.3 KO (knockout) mice. KU-32 is readily bioavailable and was administered once a week for 6 weeks at a dose of 20 mg/kg to WT and Hsp70 KO mice that had been rendered diabetic with streptozotocin for 12 weeks. After 12 weeks of diabetes, both WT and Hsp70 KO mice developed deficits in NCV (nerve conduction velocity) and a sensory hypoalgesia. Although KU-32 did not improve glucose levels, HbA1c (glycated haemoglobin) or insulin levels, it reversed the NCV and sensory deficits in WT but not Hsp70 KO mice. These studies provide the first evidence that targeting molecular chaperones reverses the sensory hypoalgesia associated with DPN.This work was supported by grants from the Juvenile Diabetes Research Foundation and the National Institutes of Health [NS054847 and DK073594] (to R.T.D.) and [CA120458 and CA109265] (to B.S.J.B.)

Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice

Increasing the expression of Hsp70 (heat-shock protein 70) can inhibit sensory neuron degeneration after axotomy. Since the onset of DPN (diabetic peripheral neuropathy) is associated with the gradual decline of sensory neuron function, we evaluated whether increasing Hsp70 was sufficient to improve several indices of neuronal function. Hsp90 is the master regulator of the heat-shock response and its inhibition can up-regulate Hsp70. KU-32 (N-{7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy]-8-methyl-2-oxo-2H-chromen-3-yl}acetamide) was developed as a novel, novobiocin-based, C-terminal inhibitor of Hsp90 whose ability to increase Hsp70 expression is linked to the presence of an acetamide substitution of the prenylated benzamide moiety of novobiocin. KU-32 protected against glucose-induced death of embryonic DRG (dorsal root ganglia) neurons cultured for 3 days in vitro. Similarly, KU-32 significantly decreased neuregulin 1-induced degeneration of myelinated Schwann cell DRG neuron co-cultures prepared from WT (wild-type) mice. This protection was lost if the co-cultures were prepared from Hsp70.1 and Hsp70.3 KO (knockout) mice. KU-32 is readily bioavailable and was administered once a week for 6 weeks at a dose of 20 mg/kg to WT and Hsp70 KO mice that had been rendered diabetic with streptozotocin for 12 weeks. After 12 weeks of diabetes, both WT and Hsp70 KO mice developed deficits in NCV (nerve conduction velocity) and a sensory hypoalgesia. Although KU-32 did not improve glucose levels, HbA1c (glycated haemoglobin) or insulin levels, it reversed the NCV and sensory deficits in WT but not Hsp70 KO mice. These studies provide the first evidence that targeting molecular chaperones reverses the sensory hypoalgesia associated with DPN

The dark matter environment of the Abell 901/902 supercluster: a weak lensing analysis of the HST STAGES survey

We present a high resolution dark matter reconstruction of the z=0.165 Abell 901/902 supercluster from a weak lensing analysis of the HST STAGES survey. We detect the four main structures of the supercluster at high significance, resolving substructure within and between the clusters. We find that the distribution of dark matter is well traced by the cluster galaxies, with the brightest cluster galaxies marking out the strongest peaks in the dark matter distribution. We also find a significant extension of the dark matter distribution of Abell 901a in the direction of an infalling X-ray group Abell 901alpha. We present mass, mass-to-light and mass-to-stellar mass ratio measurements of the structures and substructures that we detect. We find no evidence for variation of the mass-to-light and mass-to-stellar mass ratio between the different clusters. We compare our space-based lensing analysis with an earlier ground-based lensing analysis of the supercluster to demonstrate the importance of space-based imaging for future weak lensing dark matter 'observations'.Comment: 13 pages, 6 figures and 4 tables. Accepted for publication in MNRA

A pandemic strain of calicivirus threatens rabbit industries in the Americas

Rabbit Hemorrhagic Disease (RHD) is a severe acute viral disease specifically affecting the European rabbit Oryctolagus cuniculus. As the European rabbit is the predominant species of domestic rabbit throughout the world, RHD contributes towards significant losses to rabbit farming industries and endangers wild populations of rabbits in Europe and other predatory animals in Europe that depend upon rabbits as a food source. Rabbit Hemorrhagic Disease virus (RHDV) – a Lagovirus belonging to the family Caliciviridae is the etiological agent of RHD. Typically, RHD presents with sudden death in 70% to 95% of infected animals. There have been four separate incursions of RHDV in the USA, the most recent of which occurred in the state of Indiana in June of 2005. Animal inoculation studies confirmed the pathogenicity of the Indiana 2005 isolate, which caused acute death and pathological changes characterized by acute diffuse severe liver necrosis and pulmonary hemorrhages. Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage. All of the USA isolates clustered with RHDV genomes from China, and phylogenetic analysis of the major capsid protein (VP60) revealed that they were related to a pandemic antigenic variant strain known as RHDVa. Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype. Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat

Path Integral Monte Carlo Approach to the U(1) Lattice Gauge Theory in (2+1) Dimensions

Path Integral Monte Carlo simulations have been performed for U(1) lattice gauge theory in (2+1) dimensions on anisotropic lattices. We extractthe static quark potential, the string tension and the low-lying "glueball" spectrum.The Euclidean string tension and mass gap decrease exponentially at weakcoupling in excellent agreement with the predictions of Polyakov and G{\" o}pfert and Mack, but their magnitudes are five times bigger than predicted. Extrapolations are made to the extreme anisotropic or Hamiltonian limit, and comparisons are made with previous estimates obtained in the Hamiltonian formulation.Comment: 12 pages, 16 figure