Super yatch design study for Malaysian sea (Langkawi Island)

Malaysia as a country surrounded by water has a huge economic and geographical potential in the development of super yacht industry in South East Asia. There is lack of super yacht design study specifying to Malaysian marinas and seas. Most of the super yacht operates in Malaysia were built and bought directly from oversea, and chartered by foreign companies. It is hence the purpose of this study to survey on Malaysian sea water, particularly Langkawi Island, to introduce a design methodology in producing a preliminary design of super yacht that suits Langkawi Island, and serves as a guideline for future super yacht design for Malaysian sea in different marinas. Suitable dimensions of super yacht were derived by using dimensional relationship via statistical method. Two types of hull form designs (round bilge and V-bottom hull) were designed using Maxsurf Pro software. Resistance analysis on the two hull forms were carried out using Savitsky Pre-Planing and Compton methods via MaxsurfHullspeed software, and stability performance of the two hull forms was analyze using Hydromax software. VBottom hull form is found to have better resistance performance as compared to round bilge hull form, and both hull forms are found to be in stable conditions and comply with IMO requirements

Single-point single-molecule FRAP distinguishes inner and outer nuclear membrane protein distribution

The normal distribution of nuclear envelope transmembrane proteins (NETs) is disrupted in several human diseases. NETs are synthesized on the endoplasmic reticulum and then transported from the outer nuclear membrane (ONM) to the inner nuclear membrane (INM). Quantitative determination of the distribution of NETs on the ONM and INM is limited in available approaches, which moreover provide no information about translocation rates in the two membranes. Here we demonstrate a single-point single-molecule FRAP microscopy technique that enables determination of distribution and translocation rates for NETs in vivo

Influence of cytoskeleton organization on recombinant protein expression by CHO cells.

In this study, we assessed the importance of cytoskeleton organization in the mammalian cells used to produce therapeutic proteins. Two cytoskeletal genes, Actin alpha cardiac muscle 1 (ACTC1) and a guanosine triphosphate GTPase-activating protein (TAGAP), were found to be upregulated in highly productive therapeutic protein-expressing Chinese hamster ovary (CHO) cells selected by the deprivation of vitamin B5. We report here that the overexpression of the ACTC1 protein was able to improve significantly recombinant therapeutic production, as well as to decrease the levels of toxic lactate metabolic by-products. ACTC1 overexpression was accompanied by altered as well as decreased polymerized actin, which was associated with high protein production by CHO cell cultured in suspension. We suggest that the depolymerization of actin and the possible modulation of integrin signaling, as well as changes in basal metabolism, may be driving the increase of protein secretion by CHO cells

Lactose-Modified Chitosan Gold(III)-PEGylated Complex-Bioconjugates: From Synthesis to Interaction with Targeted Galectin-1 Protein

Galectins (Gal) are a family of glycan-binding proteins characterized by their affinity for \u3b2-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Coordination chemistry has been engaged to develop versatile multivalent neoglycoconjugates for binding Gal-1. In this study we report a fast and original method to synthesize hybrid gold nanoparticles in which a hydrochloride\ua0lactose-modified chitosan, named CTL, is mixed with dicarboxylic acid-terminated polyethylene glycol (PEG), leading to shell-like hybrid polymer-sugar-metal nanoparticles (CTL-PEG-AuNPs). The aim of this paper is to preliminarily study the interaction of the CTL-PEG-AuNPs with a target protein, namely, Gal-1, under specific conditions. The molecular interaction has been measured by Transmission Electron Microscopy (TEM), UV-vis, and Raman Spectroscopy on a large range of Gal-1 concentrations (from 0 to 10-12 M). We observed that the interaction was strongly dependent on the Gal-1 concentration at the surface of the gold nanoparticles

Characterization and mutagenesis of Chinese hamster ovary cells endogenous retroviruses to inactivate viral particle release.

The Chinese hamster ovary (CHO) cells used to produce biopharmaceutical proteins are known to contain type-C endogenous retrovirus (ERV) sequences in their genome and to release retroviral-like particles. Although evidence for their infectivity is missing, this has raised safety concerns. As the genomic origin of these particles remained unclear, we characterized type-C ERV elements at the genome, transcriptome, and viral particle RNA levels. We identified 173 type-C ERV sequences clustering into three functionally conserved groups. Transcripts from one type-C ERV group were full-length, with intact open reading frames, and cognate viral genome RNA was loaded into retroviral-like particles, suggesting that this ERV group may produce functional viruses. CRISPR-Cas9 genome editing was used to disrupt the gag gene of the expressed type-C ERV group. Comparison of CRISPR-derived mutations at the DNA and RNA level led to the identification of a single ERV as the main source of the release of RNA-loaded viral particles. Clones bearing a Gag loss-of-function mutation in this ERV showed a reduction of RNA-containing viral particle release down to detection limits, without compromising cell growth or therapeutic protein production. Overall, our study provides a strategy to mitigate potential viral particle contaminations resulting from ERVs during biopharmaceutical manufacturing

Cerebrospinal Fluid Glucose and Lactate Levels after Subarachnoid Hemorrhage: A Multicenter Retrospective Study

Background:In patients with subarachnoid hemorrhage (SAH), abnormalities in glucose and lactate metabolism have been described using cerebral microdialysis. Glucose and lactate concentrations in cerebrospinal fluid (CSF) are more easily accessible, but scarce data are available in this setting. The aim of this study is to assess the relationship of CSF glucose and lactate with blood concentrations and with unfavorable neurological outcome after SAH.Methods:A retrospective cohort study was conducted in 5 European University intensive care units. Patients aged 18 years and above who were admitted after a nontraumatic SAH over a 4-year period (2011 to 2014) were included if they had an external ventricular drain placed, daily analysis of CSF including glucose (±lactate) concentrations for 1 to 4 consecutive days, and concomitant analysis of glucose and lactate concentrations in the arterial blood.Results:A total of 144 patients were included in the final analysis (median age: 58 [49 to 66] y; male sex: 77/144). Median time from admission to external ventricular drain placement was 1 (0 to 3) day; median Glasgow Coma Scale on admission was 10 (7 to 13), and CT-scan Fisher scale was 4. A total of 81 (56%) patients had unfavorable neurological outcome at 3 months (Glasgow Outcome Scale ≤3). There was a weak correlation between blood and CSF glucose (r2=0.07, P=0.007), and between blood and CSF lactate levels (r2=0.58, P<0.001) on day 1, which were not influenced by insulin therapy. The presence of shock and low CSF glucose/lactate ratio were the only independent predictors of unfavorable outcome.Conclusions:CSF glucose and lactate levels poorly correlated with blood concentrations. Low CSF glucose/lactate ratio was associated with poor neurological outcome

A multinational audit of small field output factors calculated by treatment planning systems used in radiotherapy

Background and purpose: An audit methodology for verifying the implementation of output factors (OFs) of small fields in treatment planning systems (TPSs) used in radiotherapy was developed and tested through a multinational research group and performed on a national level in five different countries. Materials and methods: Centres participating in this study were asked to provide OFs calculated by their TPSs for 10 × 10 cm2, 6 × 6 cm2, 4 × 4 cm2, 3 × 3 cm2 and 2 × 2 cm2 field sizes using an SSD of 100 cm. The ratio of these calculated OFs to reference OFs was analysed. The action limit was ±3% for the 2 × 2 cm2 field and ±2% for all other fields. Results: OFs for more than 200 different beams were collected in total. On average, the OFs for small fields calculated by TPSs were generally larger than measured reference data. These deviations increased with decreasing field size. On a national level, 30% and 31% of the calculated OFs of the 2 × 2 cm2 field exceeded the action limit of 3% for nominal beam energies of 6 MV and for nominal beam energies higher than 6 MV, respectively. Conclusion: Modern TPS beam models generally overestimate the OFs for small fields. The verification of calculated small field OFs is a vital step and should be included when commissioning a TPS. The methodology outlined in this study can be used to identify potential discrepancies in clinical beam models. Keywords: Dosimetry audit, Small field output factors, Treatment planning syste