CRANKITE: a fast polypeptide backbone conformation sampler

Background: CRANKITE is a suite of programs for simulating backbone conformations of polypeptides and proteins. The core of the suite is an efficient Metropolis Monte Carlo sampler of backbone conformations in continuous three-dimensional space in atomic details. Methods: In contrast to other programs relying on local Metropolis moves in the space of dihedral angles, our sampler utilizes local crankshaft rotations of rigid peptide bonds in Cartesian space. Results: The sampler allows fast simulation and analysis of secondary structure formation and conformational changes for proteins of average length

Pregnancy related breast diseases in a developing African country: Initial Sonographic Evaluation

Benign diseases are more common than malignant diseases in pregnant and lactating women. Fibroadenomas are the most commonly identifiedbenign breast tumour in pregnant and lactating women. Pregnancy related breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at 1 in 3000 to 1 in 10 000 pregnancies. Several reproductive factors like age at menarche, age at menopause, age at full-term pregnancy, parity, age at any birth and spacing of pregnancies, breast feeding, characteristics of the menstrual cycle, infertility, spontaneous and induced abortions, characteristics of the menstrual cycle and infertility are some of the factors that have been incriminated as risk factors for breast cancer. We sought to describe the predominant breast pattern, sonographic array of pregnancy related breast diseases in women referred to the breast imaging unit in the department of Radiology at the University College Hospital, Ibadan south west Nigeria. Socio-demographic characteristics in these women were also evaluated. Archived images were reviewed and documented and data was analysed with SPSS version 17 and presented with descriptives. In this descriptive study, we retrospectively retrieved the sonomammographic records of 21 women (pregnant or lactating) referred to and imaged in the department of radiology, University college hospital Ibadan, between 2006 and 2013. Diagnostic breast sonograms performed by MO and ATS; Consultant  radiologists with 7-10 years' experience utilized a 7-10 MHz transducer of the General electric GE Logiq P5 machine for the scans. Twenty-one women with ages between 22-42 years (Mean 31.4 ±5.4 SD) pregnant or lactating were referred to the radiology department for sonomammographic  evaluation. Majority of the women were in the 3rd decade. Referral was mainly (11) by family Physicians from the general outpatient clinic, 5 were self-referred, 2 from radiotherapy department, 2 from obstetrics and gynaecology department and 1 from the surgical outpatient clinic. Nineteen (89.5%) were lactating and breastfeeding while 2 (10.5%) were pregnant. Nipple discharge (89.5%) was the predominant presenting complaint in the study. They were all married with the majority attaining menarche at age 14.6±2.1 SD years. Most of the women were multi-parous 17(89.5%) and possessed higher level of Education 17 (81.0%). Twenty (96.0%) women had no previous breast disease while only 1 (4.0%) woman had a positive family history of breast cancer. They weighed between 44-102kg (mean 69.84kg±15.33SD). Their mean height was 159.8cm. Waist hip ratio was between 0.69-0.93 (Mean 0.83). The heterogeneous fibroglandular pattern was predominant in 15 (71.4%) women. Final BIRADS assessment of 2 was most frequent (11/21) 52.4% while 19.0% were assigned to BIRADS categories 0 and 1 (4/21). Histological diagnosis of Invasive ductal  carcinoma was made in the 3 women with final BIRADS of 5 breast diseases found in most pregnant and lactating women were benign. It is important to note that malignant breast lesions can also occur in this group of women who may assume that the changes noted in their breast are due to  lactation

Proximate and Mineral Elements Composition of Three Forest Fruits Sold in Port Harcourt, Nigeria

This study aimed to assess the nutritional and trace elements composition of selected forest fruits sold for human consumption in Port Harcourt. Fruit contamination by heavy metals is an issue of global concern. Nondegradable elements bioaccumulations in tissues and organs have deleterious effects in man. Three (3) Agroforestry fruits species; (Spondias cytherea L. (Anacardiaceae), Syzygium malaccense (L.) Merr. & L. M. Perry Myrtaceae and Cola pachycarpa K. Schum. Malvaceae) were purposefully selected and sourced from three strategically located markets namely; Oil mill, Choba and D/line fruit markets. The fruit species were procured and washed with distilled water and the edible parts extracted, chopped and sun dried properly. The nutritional composition was analyzed using 18th edition of the Association of Official Analytical Chemist while trace metals were analysed using PIXE Accelerator. Spondias cytherea yielded high percentage of crude Protein (8.373±0.1) and Fibre content (11.73±0.03), while Syzygium malaccense was rich in Fat (7.17±0.02) and Ash (4.17±0.04). Moisture content was highest in Cola parchycarpa (12.63±0.05). PIXE Accelerator analysis revealed that the fruits contain high concentration of trace metals; S. malaccense contained Mg (1170±237.0ppm), Si (60.02±68.95ppm), Al (14.89±7.71ppm), Fe (10. 60±4.11ppm), Rb (3.20±0.00ppm) and Ti (1.82±0.00ppm). C. parchycarpa had Zn (6.22±11.80ppm), Cr (1.60±0.75 ppm), Mn (0. 71±0.87ppm) and Cu (0.38±0.33ppm). Ni (0.16 ppm) was found only in S. cytherea fruit. The forest fruits are rich in nutrients vital for healthy growth but the level of heavy metals (Mg, Al. Cr, Fe and Zn) in each of the fruits were above WHO/FAO permissible limit, therefore excessive consumption on a daily/weekly routine should be avoided. Keywords: Forest fruits, proximate, heavy metals, human healt

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

ENGINEERING BIOCERAMIC MICROSTRUCTURE FOR CUSTOMIZED DRUG DELIVERY

One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are a-cristobalite (SiO2, Cris) and ß- rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and the release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated the high affinity between the P-O functional groups, in Rhe and SCPC, and the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 µg Vanc/m2 for Rhe > 4.49 µg Vanc /m2 for SCPC>3.01 µg Vanc /m2 for Cris (p<0.05). Cis loading capacity increased in the order 8.59 µg Vanc /m2 for Cris, 17.8 µg Vanc/m2 for Rhe and 6.03 µg Vanc /m2 for SCPC (p<0.05). The drug release kinetics was dependent on the carrier as well as on the kind of drug. Different burst release and sustained release rates were measured for Vanc and Cis from the same carrier. The percentages of the amount of drug amount released from Cris, Rhe and SCPC during the burst stage (the first 2h) were: 50%, 50%, and 46% of Vanc; and 53.4%, 36.6%, and 30.6 % of Cis, respectively. Burst release correlated with the pore size distribution and surface area. Furthermore, the average rates of sustained release in the period 8-216h from Cris, Rhe and SCPC were: 9.8, 7.2 and 3.5 µg/h of Vanc and 4.5, 5.3 and 3.5 µg/h of Cis, respectively. Nearly inert Cris ceramic showed release kinetics controlled by its hierarchical nanoporous structure. On the other hand, the phase composition and surface chemistry of bioactive Rhe or SCPC ceramics overruled the effect of surface area. The relatively low rate of drug release from SCPC was due to the dissolution-back precipitation reaction taking place on the material surface as confirmed by FTIR bands of surface hydroxyapatite layer at 576.5, 596.7 and 620.7 cm-1. Moreover, the solid solution of crystalline phases of SCPC enhanced the bioactivity of the composite. Nuclear Magnetic Resonance (NMR) and cell culture analyses demonstrated that the interactions between the SCPC dissolution products and the released drug did not cause measurable negative effects on the bioactivity of the tested drugs. The therapeutic effects of the SCPC-Cis hybrid were evaluated using a rat model of hepatocellular carcinoma (HCC). Animals were treated by either systemic cisplatin injection (sCis), or with SCPC-Cis hybrid placed adjacent (ADJ) to, or within (IT), the tumor. Five days after implantation 50-55% of the total cisplatin loaded was released from the SCPC-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared to sCis treatment. Severe side effects were observed in animals treated with sCis including rapid weight loss and decreased liver and kidney function; such effects were not observed in SCPC-Cis treated animals. Analysis of cisplatin distribution demonstrated drug concentrations in the tumor were 21 and 1.5-times higher in IT and ADJ groups, respectively, as compared to sCis treated animals. These data demonstrate the SCPC drug delivery system can provide an effective localized treatment for HCC with significantly reduced toxicity compared to systemic drug administration. Moreover, it is possible to tailor drug release kinetics from SCPC hybrids by controlling the crystalline structure of the material and the ratios of Cris and Rhe in the composite

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Proximate and Mineral Elements Composition of Three Forest Fruits Sold in Port Harcourt, Nigeria

This study aimed to assess the nutritional and trace elements composition of selected forest fruits sold for human consumption in Port Harcourt. Fruit contamination by heavy metals is an issue of global concern. Nondegradable elements bioaccumulations in tissues and organs have deleterious effects in man. Three (3) Agroforestry fruits species; ( Spondias cytherea L. (Anacardiaceae), Syzygium malaccense (L.) Merr. & L. M. Perry Myrtaceae and Cola pachycarpa K. Schum. Malvaceae) were purposefully selected and sourced from three strategically located markets namely; Oil mill, Choba and D/line fruit markets. The fruit species were procured and washed with distilled water and the edible parts extracted, chopped and sun dried properly. The nutritional composition was analyzed using 18th edition of the Association of Official Analytical Chemist while trace metals were analysed using PIXE Accelerator. Spondias cytherea yielded high percentage of crude Protein (8.373\ub10.1) and Fibre content (11.73\ub10.03), while Syzygium malaccense was rich in Fat (7.17\ub10.02) and Ash (4.17\ub10.04). Moisture content was highest in Cola parchycarpa (12.63\ub10.05). PIXE Accelerator analysis revealed that the fruits contain high concentration of trace metals; S. malaccense contained Mg (1170\ub1237.0ppm), Si (60.02\ub168.95ppm), Al (14.89\ub17.71ppm), Fe (10. 60\ub14.11ppm), Rb (3.20\ub10.00ppm) and Ti (1.82\ub10.00ppm). C. parchycarpa had Zn (6.22\ub111.80ppm), Cr (1.60\ub10.75 ppm), Mn (0. 71\ub10.87ppm) and Cu (0.38\ub10.33ppm). Ni (0.16 ppm) was found only in S. cytherea fruit. The forest fruits are rich in nutrients vital for healthy growth but the level of heavy metals (Mg, Al. Cr, Fe and Zn) in each of the fruits were above WHO/FAO permissible limit, therefore excessive consumption on a daily/weekly routine should be avoided

The ethical desirability of moral bioenhancement: A review of reasons

Background: The debate on the ethical aspects of moral bioenhancement focuses on the desirability of using biomedical as opposed to traditional means to achieve moral betterment. The aim of this paper is to systematically review the ethical reasons presented in the literature for and against moral bioenhancement. Discussion: A review was performed and resulted in the inclusion of 85 articles. We classified the arguments used in those articles in the following six clusters: (1) why we (don't) need moral bioenhancement, (2) it will (not) be possible to reach consensus on what moral bioenhancement should involve, (3) the feasibility of moral bioenhancement and the status of current scientific research, (4) means and processes of arriving at moral improvement matter ethically, (5) arguments related to the freedom, identity and autonomy of the individual, and (6) arguments related to social/group effects and dynamics. We discuss each argument separately, and assess the debate as a whole. First, there is little discussion on what distinguishes moral bioenhancement from treatment of pathological deficiencies in morality. Furthermore, remarkably little attention has been paid so far to the safety, risks and side-effects of moral enhancement, including the risk of identity changes. Finally, many authors overestimate the scientific as well as the practical feasibility of the interventions they discuss, rendering the debate too speculative. Summary: Based on our discussion of the arguments used in the debate on moral enhancement, and our assessment of this debate, we advocate a shift in focus. Instead of speculating about non-realistic hypothetical scenarios such as the genetic engineering of morality, or morally enhancing 'the whole of humanity', we call for a more focused debate on realistic options of biomedical treatment of moral pathologies and the concrete moral questions these treatments raise

Pathways of Early Fatherhood, Marriage, and Employment: A Latent Class Growth Analysis

http://dx.doi.org/10.1007/s13524-011-0022-