NaI (Tl) Calorimeter Calibration and Simulation for Coulomb Sum Rule Experiment in Hall-A at Jefferson Lab

A precision measurment of inclusive electron scattering cross sections was carried out at Jefferson Lab in the quasi-elastic region for ${^4}$He, ${^{12}}$C, ${^{56}}$Fe and ${^{208}}$Pb targets. Longitudinal ($R_{L}$) and transverse ($R_{T}$) response functions of nucleon were extracted in the momentum transfer range 0.55 GeV/c$\le$$|q|$$\le$1.0 GeV/c. To achieve the above goal, a NaI (Tl) calorimeter was used to distinguish good electrons from background including pions and low energy electrons rescattered from walls of the spectrometer magnets. Due to a large set of kinematics and changes in HV settings, a number of calibrations were performed for the NaI (Tl) detector. Corrections for a few blocks of NaI (Tl) with bad or no signal were applied. The resolution of NaI (Tl) detector after calibration reached $\frac{\delta E}{\sqrt{E}} \approx 3\%$ at E=1 GeV. The performance of NaI (Tl) detector was compared with a simulation

(E)-2-Bromo-4-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino­meth­yl]-6-meth­oxy­phenyl 4-methyl­benzene­sulfonate

In the title compound, C26H24BrN3O5S, the central benzene ring makes dihedral angles of 6.27 (6), 33.63 (6) and 69.31 (5)°, respectively, with the pyrazolone ring, the bromo­benzene ring and the terminal phenyl ring. An intra­molecular C—H⋯O hydrogen bond occurs. The crystal packing features weak non-classical C—Br⋯O inter­actions [Br⋯O = 3.222 (2) Å] that form inversion-related dimers

Role of TNF-α in vascular dysfunction

Healthy vascular function is primarily regulated by several factors including EDRF (endothelium-dependent relaxing factor), EDCF (endothelium-dependent contracting factor) and EDHF (endothelium-dependent hyperpolarizing factor). Vascular dysfunction or injury induced by aging, smoking, inflammation, trauma, hyperlipidaemia and hyperglycaemia are among a myriad of risk factors that may contribute to the pathogenesis of many cardiovascular diseases, such as hypertension, diabetes and atherosclerosis. However, the exact mechanisms underlying the impaired vascular activity remain unresolved and there is no current scientific consensus. Accumulating evidence suggests that the inflammatory cytokine TNF (tumour necrosis factor)-α plays a pivotal role in the disruption of macrovascular and microvascular circulation both in vivo and in vitro. AGEs (advanced glycation end-products)/RAGE (receptor for AGEs), LOX-1 [lectin-like oxidized low-density lipoprotein receptor-1) and NF-κB (nuclear factor κB) signalling play key roles in TNF-α expression through an increase in circulating and/or local vascular TNF-α production. The increase in TNF-α expression induces the production of ROS (reactive oxygen species), resulting in endothelial dysfunction in many pathophysiological conditions. Lipid metabolism, dietary supplements and physical activity affect TNF-α expression. The interaction between TNF-α and stem cells is also important in terms of vascular repair or regeneration. Careful scrutiny of these factors may help elucidate the mechanisms that induce vascular dysfunction. The focus of the present review is to summarize recent evidence showing the role of TNF-α in vascular dysfunction in cardiovascular disease. We believe these findings may prompt new directions for targeting inflammation in future therapies

2-Ferrocenyl-3-meth­oxy-6-methyl­pyridine

In the title compound, [Fe(C5H5)(C12H12NO)], the dihedral angle between the pyridyl and substituted cyclo­penta­dienyl rings is 23.58 (3)°. The crystal structure is characterized by weak inter­molecular C—H⋯N hydrogen-bonding contacts, leading to the formation of chains running parallel to the n-glide planes. A weak inter­molecular C—H⋯π contact is also present

Structural and molecular basis for the substrate positioning mechanism of a new PL7 subfamily alginate lyase from the Arctic

Alginate lyases play important roles in alginate degradation in the ocean. Although a large number of alginate lyases have been characterized, little is yet known about those in extremely cold polar environments, which may have unique mechanisms for environmental adaptation and for alginate degradation. Here, we report the characterization of a novel PL7 alginate lyase AlyC3 from Psychromonas sp. C-3 isolated from the Arctic brown alga Laminaria, including its phylogenetic classification, catalytic properties and structure. We propose the establishment of a new PM-specific subfamily of PL7 (subfamily 6) represented by AlyC3 based on phylogenetic analysis and enzymatic properties. Structural and biochemical analyses showed that AlyC3 is a dimer, representing the first dimeric endo-alginate lyase structure. AlyC3 is activated by NaCl and adopts a novel salt-activated mechanism, that is, salinity adjusts the enzymatic activity by affecting its aggregation states. We further solved the structure of an inactive mutant H127A/Y244A in complex with a dimannuronate molecule, and proposed the catalytic process of AlyC3 based on structural and biochemical analyses. We show that Arg82 and Tyr190 at the two ends of the catalytic canyon help the positioning of the repeated units of the substrate, and that His127, Tyr244, Arg78, and Gln125 mediate the catalytic reaction. Our study uncovers, for the first time, the amino acid residues for alginate positioning in an alginate lyase, and demonstrate that such residues involved in alginate positioning are conserved in other alginate lyases. This study provides a better understanding of the mechanisms of alginate degradation by alginate lyases

Pharmacokinetic Interaction between Magnolol and Piperine in Rats

Purpose: To investigate the pharmacokinetic mechanism of interaction between magnolol and piperine when co-administered to rats.Methods: The rats were divided into five groups as follows: magnolol group (625 mg/kg); low dose of piperine group (20 mg/kg); high dose of piperine group (40 mg/kg); low dose of piperine + magnolol group; or high dose of piperine + magnolol group. Plasma samples were collected at regular time intervals after administration of a single dose of magnolol (625 mg/kg, p.o.) alone or piperine (20 or 40 mg/kg, p.o.) in the presence or absence of magnolol (625 mg/kg, p.o.). The concentrations of magnolol and piperine in plasma were measured by a validated high performance liquid chromatography (HPLC) method.Results: Compared with control, the groups given magnolol alone, concomitant administration of piperine and magnolol resulted in significant decrease (p < 0.01) in the AUC and Cmax of magnolol. Interestingly, compared with administration of piperine alone (20 mg/kg), co-administration with magnolol did not significantly (p > 0.05) alter the pharmacokinetic parameters of piperine. However, at high dose (40 mg/kg) of piperine, Cmax of piperine significantly decreased from 4.30 ± 1.47 to 2.50 ± 0.78 μg/mL (p < 0.05).Conclusion: Co-administration of magnolol and piperine decreases plasma concentration of either drug in rats, suggesting that concurrent use of magnolol with piperine or piperine-containing diets would require close monitoring for potential interactions.Keywords: Magnolol, Piperine, Pharmacokinetic interaction, Co administratio

Characterization of a cryptic plasmid pSM429 and its application for heterologous expression in psychrophilic Pseudoalteromonas

<p>Abstract</p> <p>Background</p> <p><it>Pseudoalteromonas </it>is an important genus widespread in marine environment, and a lot of psychrophilic <it>Pseudoalteromonas </it>strains thrive in deep sea and polar sea. By now, there are only a few genetic systems for <it>Pseudoalteromonas </it>reported and no commercial <it>Pseudoalteromonas </it>genetic system is available, which impedes the study of <it>Pseudoalteromonas</it>, especially for psychrophilic strains. The aim of this study is to develop a heterologous expression system for psychrophilic <it>Pseudoalteromonas</it>.</p> <p>Results</p> <p>A cryptic plasmid pSM429 isolated from psychrophilic <it>Pseudoalteromonas </it>sp. BSi20429 from the Arctic sea ice, was sequenced and characterized. The plasmid pSM429 is 3874 bp in length, with a G+C content of 28%. Four putative open reading frames (ORFs) were identified on pSM429. Based on homology, the ORF4 was predicted to encode a replication initiation (Rep) protein. A shuttle vector (<it>Escherichia coli, Pseudoalteromonas</it>), pWD, was constructed by ligating pSM429 and pUC19 and inserting a chloramphenicol acetyl transferase (CAT) cassette conferring chloramphenicol resistance. To determine the minimal replicon of pSM429 and to check the functionality of identified ORFs, various pWD derivatives were constructed. All derivatives except the two smallest ones were shown to allow replication in <it>Pseudoalteromonas </it>sp. SM20429, a plasmid-cured strain of <it>Pseudoalteromonas </it>sp. BSi20429, suggesting that the <it>orf4 </it>and its flanking intergenic regions are essential for plasmid replication. Although not essential, the sequence including some repeats between <it>orf1 </it>and <it>orf2 </it>plays important roles in segregational stability of the plasmid. With the aid of pWD-derived plasmid pWD2, the erythromycin resistance gene and the <it>cd </it>gene encoding the catalytic domain of a cold-adapted cellulase were successfully expressed in <it>Pseudoalteromonas </it>sp. SM20429.</p> <p>Conclusions</p> <p>Plasmid pSM429 was isolated and characterized, and the regions essential for plasmid replication and stability were determined, helping the development of pSM429-based shuttle vectors. The shuttle vectors pWD and its derivatives could be used as cloning vectors for <it>Pseudoalteromonas</it>, offering new perspectives in the genetic manipulation of <it>Pseudoalteromonas </it>strains. With the aid of pWD-derived vector and its host, the erythromycin resistance gene and the <it>cd </it>gene of a cold-adapted protein were successfully expressed, indicating that the potential use of this system for recombinant protein production, especially for cold-adapted proteins.</p

Association of hematological parameters with metabolic syndrome in Beijing adult population: a longitudinal study

The purposes of the study were to estimate the incidence of metabolic syndrome (MetS) and to systematically evaluate the relationship between hematological parameters and MetS in a 5-year follow-up of Beijing adult population. The longitudinal study included 3,180 adults, aged 20–65 years, who attended health check-ups in Beijing Tongren Hospital in 2007 and 2012. Multivariate logistic regression was conducted to explore the associations between hematological parameters and MetS. The 5-year cumulative incidence of MetS in this sample was 10.82 % (14.22 % for males and 7.59 % for females). Among all the hematological parameters, white blood cell count (WBC) was positively associated with MetS for 20–35-year-old (male OR 1.482, 95 % CI 1.169–2.974; female OR 1.398, 95 % CI 1.145–3.011), and 36–50-year-old (male OR 2.012, 95 % CI 1.290–4.010; female OR 3.400, 95 % CI 1.818–4.528) male and female subjects. Alanine aminotransferase (ALT) was significantly associated with the incidence of MetS for males (20–35-year-old OR 2.080, 95 % CI 1.371–3.159; 36–50-year-old OR 2.421, 95 % CI 1.335–3.412; 51–65-year-old OR 4.267, 95 % CI 1.161–6.781). Low-density lipoprotein cholesterol (LDL-C) was positively associated with MetS for 51–65-year-old (male OR 3.078, 95 % CI 2.468–5.131; female OR 2.140, 95 %CI 1.524–4.359) for male and female subjects. WBC is positively associated with MetS for young adults, while LDL-C is positively associated with MetS for elderly people. ALT is positively associated with MetS for males. Our findings provide further evidence in support of using hematological markers for early detection of individuals at risk for MetS

Risk factors of distant brain failure for patients with newly diagnosed brain metastases treated with stereotactic radiotherapy alone

<p>Abstract</p> <p>Objective</p> <p>To explore the risk factors of distant brain failure (DBF) for patients with brain metastasis (BM) who were treated with stereotactic radiotherapy alone and to group the patients on the basis of their risk levels.</p> <p>Methods and Materials</p> <p>We retrospectively analyzed 132 newly diagnosed BM patients who were treated with stereotactic radiotherapy alone from May 2000 to April 2010. Kaplan-Meier and Cox proportional hazards regression analyses were performed for univariate and multivariate analyses.</p> <p>Results</p> <p>The 1-year incidence rate of DBF was 44.7%, and the median DBF time (MDBFT) was 18 months. In multivariate analysis, the risk factors of DBF were the number of BMs greater than 1 (p = 0.041), uncontrolled extracranial disease (p = 0.005), interval time (IT) of less than 60 months between the diagnosis of primary tumor and BM (p = 0.024), and total volume of BM was greater than 6 cc (p = 0.049). Each risk factor was assigned 1 score. The median survival times for the patients with scores of 0-1, 2-3, and 4 were 31, 12, and 10 months, respectively, and the corresponding MDBFTs were not reached, 13, and 3 months, respectively, (p < 0.001). The crude DBF incidence rates in patients with scores of 0-1, 2-3, and 4 were 14.8%, 50.0%, and 76.9%, respectively, (p < 0.001).</p> <p>Conclusions</p> <p>The patients with scores of 0-1 had a lower risk of DBF than the patients with higher scores did, and it may be reasonable to treat these patients with SRS alone and resort to whole-brain radiation therapy only for salvage. The patients with a score of 4 had the highest risk of developing DBF after stereotactic radiotherapy alone, these patients may be candidates for initial whole-brain radiation therapy or clinical trials. The patients with a score of 2-3 had a moderate risk of developing DBF, SRT alone combined with close clinical monitoring would be the optimal treatment regimen for such patients, and for those patients with difficulties in receiving close clinical mornitoring, SRT combined with WBRT will be more suitable.</p