Dipicolinic acid as a novel spore-inspired excipient for antibody formulation

Ionic excipients are commonly used in aqueous therapeutic monoclonal antibody (mAb) formulations. Novel excipients are of industrial interest, with a recent focus on Arg salt forms and their application as viscosity reducing and stabilizing additives. Here, we report that the calcium salt of dipicolinic acid (DPA, pyridine-2,6-dicarboxylic acid), uniquely present in nature in the core of certain bacterial spores, reduces the viscosity of a mAb formulated at 150mg/mL, below that achieved by Arg hydrochloride at the same concentration (10mM). DPA also reduced the reversible phase separation of the same formulation, which characteristically occurs for this mAb upon cooling to 4°C. Differential scanning calorimetry and differential scanning fluorimetry did not reveal a conformation destabilisation of the mAb in the presence of 10mM DPA, or by the related quinolinic acid (QA, pyridine-2,3-dicarboxylic acid). However, fluorescence spectrophotometry did reveal localised (aromatic) conformational changes to the mAb attributed to DPA, dependent on the salt form. While precise mechanisms of action remain to be identified, our preliminary data suggest that these DPA salts are worthy of further investigation as novel ionic excipient for biologics formulation.MedImmun

Levels and patterns of organochlorine pesticides in agricultural soils in an area of extensive historical cotton cultivation in Henan province, China

Organochlorine pesticides (OCPs) have attracted widespread concern because of their environmental persistence and toxicity. The historical influence of different agricultural land use types on soil concentrations of OCP residues was investigated by collecting a total of 52 surface soil samples from long-term cotton fields and fields with other crops in Lvdian township, Henan province, eastern central China. The concentration, composition, and possible sources of 16 OCPs were determined and a health risk assessment of these soils was conducted. Hexachlorocyclohexane (HCH), heptachlor, chlordane, and dichloro diphenyl trichloroethane plus its main metabolites (DDTs) were the most frequently detected OCPs with concentrations of 2.9-56.4 ng g(-1), 4.3-14.0 ng g(-1), 18.0-1254.4 ng g(-1), and below detection limit (BDL) -206.1 ng g(-1), respectively. Analysis of variance of p,p-DDE shows significant (P < 0.05) differences while other OCPs show no significant differences between historical cotton fields and fields containing other crops. Compositional analysis suggests that the HCH is derived mainly from the use of lindane and that there are recent inputs. Analysis of variance and compositional analysis indicate that the p,p-DDE in surface soil from long-term cotton fields is derived mainly from the aerobic biodegradation of historical residues. The sum of carcinogenic risk values of OCPs for soil samples were found to be 1.58 x 10(-6), posing a low cancer risk to the inhabitants of the region studied

Central synapses release a resource-efficient amount of glutamate.

Why synapses release a certain amount of neurotransmitter is poorly understood. We combined patch-clamp electrophysiology with computer simulations to estimate how much glutamate is discharged at two distinct central synapses of the rat. We found that, regardless of some uncertainty over synaptic microenvironment, synapses generate the maximal current per released glutamate molecule while maximizing signal information content. Our result suggests that synapses operate on a principle of resource optimization

Carcinoma Arising from Brunner's Gland in the Duodenum after 17 Years of Observation – A Case Report and Literature Review

A 60-year-old man presented with melena and hematemesis in 1984. Esophagogastroduodenoscopy (EGD) detected a small protruding lesion in the duodenal bulb, which was diagnosed as Brunner's adenoma. No significant change was detected in subsequent annual EGD and biopsies for 10 years, after which the patient was not observed for 7 years. The patient presented with melena again in 2001. The lesion had changed shape to become a 10 mm sessile tumor with a central depression, and following a biopsy was diagnosed as an adenocarcinoma. The patient underwent partial resection of the duodenum. Histopathological assessment showed acidophilic cells with swollen nuclei, and clear cells forming a tubular or papillary tubule in the mucosal lamina propria and submucosal layer. The tumor cells stained positive for lysozyme, indicating that they arose from Brunner's gland. The patient showed no sign of recurrence and was disease-free for more than 34 months after surgery. The patient died of pneumonia. This is an extremely rare case of primary duodenal carcinoma arising from Brunner's gland in a patient observed for 17 years

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV

The results from the STAR Collaboration on directed flow (v_1), elliptic flow (v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a Blast Wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v_2, scaling with the number of constituent quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures modified, but data the same. However, in Fig. 35 the hydro calculations are corrected in this version. The data tables are available at http://www.star.bnl.gov/central/publications/ by searching for "flow" and then this pape

Phylogenetic analysis, based on EPIYA repeats in the cagA gene of Indian Helicobacter pylori, and the implications of sequence variation in tyrosine phosphorylation motifs on determining the clinical outcome

The population of India harbors one of the world’s most highly diverse gene pools, owing to the influx of successive waves of immigrants over regular periods in time. Several phylogenetic studies involving mitochondrial DNA and Y chromosomal variation have demonstrated Europeans to have been the first settlers in India. Nevertheless, certain controversy exists, due to the support given to the thesis that colonization was by the Austro-Asiatic group, prior to the Europeans. Thus, the aim was to investigate pre-historic colonization of India by anatomically modern humans, using conserved stretches of five amino acid (EPIYA) sequences in the cagA gene of Helicobacter pylori. Simultaneously, the existence of a pathogenic relationship of tyrosine phosphorylation motifs (TPMs), in 32 H. pylori strains isolated from subjects with several forms of gastric diseases, was also explored. High resolution sequence analysis of the above described genes was performed. The nucleotide sequences obtained were translated into amino acids using MEGA (version 4.0) software for EPIYA. An MJ-Network was constructed for obtaining TPM haplotypes by using NETWORK (version 4.5) software. The findings of the study suggest that Indian H. pylori strains share a common ancestry with Europeans. No specific association of haplotypes with the outcome of disease was revealed through additional network analysis of TPMs

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

Efficacy of an Educational Material on Second Primary Cancer Screening Practice for Cancer Survivors: A Randomized Controlled Trial

<div><h3>Background</h3><p>Cancer surivors have limited knowledge about second primary cancer (SPC) screening and suboptimal rates of completion of screening practices for SPC. Our objective was to test the efficacy of an educational material on the knowledge, attitudes, and screening practices for SPC among cancer survivors.</p> <h3>Methods</h3><p>Randomized, controlled trial among 326 cancer survivors from 6 oncology care outpatient clinics in Korea. Patients were randomized to an intervention or an attention control group. The intervention was a photo-novel, culturally tailored to increase knowledge about SPC screening. Knowledge and attitudes regarding SPC screening were assessed two weeks after the intervention, and screening practices were assessed after one year.</p> <h3>Results</h3><p>At two weeks post-intervention, the average knowledge score was significantly higher in the intervention compared to the control group (0.81 vs. 0.75, P<0.01), with no significant difference in their attitude scores (2.64 vs. 2.57, P = 0.18). After 1 year of follow-up, the completion rate of all appropriate cancer screening was 47.2% in both intervention and control groups.</p> <h3>Conclusion</h3><p>While the educatinal material was effective for increasing knowledge of SPC screening, it did not promote cancer screening practice among cancer survivors. More effective interventions are needed to increase SPC screening rates in this population.</p> <h3>Trial Registration</h3><p>ClinicalTrial.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00948337">NCT00948337</a></p> </div

Modelling Vesicular Release at Hippocampal Synapses

We study local calcium dynamics leading to a vesicle fusion in a stochastic, and spatially explicit, biophysical model of the CA3-CA1 presynaptic bouton. The kinetic model for vesicle release has two calcium sensors, a sensor for fast synchronous release that lasts a few tens of milliseconds and a separate sensor for slow asynchronous release that lasts a few hundred milliseconds. A wide range of data can be accounted for consistently only when a refractory period lasting a few milliseconds between releases is included. The inclusion of a second sensor for asynchronous release with a slow unbinding site, and thereby a long memory, affects short-term plasticity by facilitating release. Our simulations also reveal a third time scale of vesicle release that is correlated with the stimulus and is distinct from the fast and the slow releases. In these detailed Monte Carlo simulations all three time scales of vesicle release are insensitive to the spatial details of the synaptic ultrastructure. Furthermore, our simulations allow us to identify features of synaptic transmission that are universal and those that are modulated by structure