Protective Emblems in Cyber Warfare

The Tallinn Manual will be released in February 2013 and makes a significant step towards defining the concepts of cyber warfare. The early draft of the manual is available and the expert working party have interpreted the existing international agreements, instruments and conventions and applied them to the field of cyber warfare. The manual makes a number of interpretations on the legal position of civilians and other parties. The manual makes it clear that the existing conventions are applicable and that civilian / religious and medical systems should be viewed as non-combatants in a cyber conflict. In the kinetic warfare environment non-combatants are indicated with recognized international symbols such as the Red Cross, Red Diamond and the Red Crescent emblems. This paper proposes a simple method in which these and other symbols for protected sites could be replicated in the cyber world with a form of digital marker to ensure that systems and traffic are recognized as being clearly protected under the same terms as those that apply to the Geneva Conventions

Preparation of Composite Electrospun Membranes Containing Strontium-Substituted Bioactive Glasses for Bone Tissue Regeneration

Barrier membranes used for the treatment of bone tissue defects caused by periodontitis lack the ability to promote new bone tissue regeneration. However, the addition of an osteogenic component to membranes may enhance their regenerative potential. Here the manufacturing of composite membranes made of poly(caprolactone) and strontium-substituted bioactive glass is described using the solution-electrospinning technique, with particles located both inside and on the surface of the fibers. All membranes are characterized using scanning electron microscopy and energy dispersive X-ray spectroscopy, and glass dissolution from within the fibers is investigated in water. In vitro material cytotoxicity is determined using a rat osteosarcoma cell line. Electrospun fibers exhibit porous surfaces and regions of increased diameter where the particles are accumulated. The glass dissolves after immersion in water, releasing dissolution products that are associated with increased pH. Further evidence suggests accelerated polymer degradation due to interactions between both components, which may provide the additional benefit of reducing the pH changes associated with glass dissolution. All compositions are biocompatible in vitro, with the exception of membranes with >50 μg of glass on their surface. In conclusion, these membranes show great potential for bone healing applications, including guided bone regeneration and scaffolds for musculoskeletal tissue engineering

FSHD muscular dystrophy Region Gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis

Facioscapulohumeral Muscular Dystrophy (FSHD) is an autosomal dominant myopathy with a strong epigenetic component. It is associated with deletion of a macrosatellite repeat leading to over-expression of the nearby genes. Among them, we focused on FSHD Region Gene 1 (FRG1) since its over-expression in mice, X. laevis and C. elegans leads to muscular dystrophy-like defects, suggesting that FRG1 plays a relevant role in muscle biology. Here we show that, when overexpressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. Moreover, Suv4-20h KO mice develop muscular dystrophy signs. Finally, we identify the FRG1/Suv4-20h1 target Eid3 as a novel myogenic inhibitor that contributes to the muscle differentiation defects. Our study suggests a novel role of FRG1 as epigenetic regulator of muscle differentiation and indicates that Suv4-20h1 has a gene-specific function in myogenesis

Copper-containing mesoporous bioactive glass promotes angiogenesis in an in vivo zebrafish model

The osteogenic and angiogenic responses of organisms to the ionic products of degradation of bioactive glasses (BGs) are being intensively investigated. The promotion of angiogenesis by copper (Cu) has been known for more than three decades. This element can be incorporated to delivery carriers, such as BGs, and the materials used in biological assays. In this work, Cu-containing mesoporous bioactive glass (MBG) in the SiO2-CaO-P2O5 compositional system was prepared incorporating 5% mol Cu (MBG-5Cu) by replacement of the corresponding amount of Ca. The biological effects of the ionic products of MBG biodegradation were evaluated on a well-known endothelial cell line, the bovine aorta endothelial cells (BAEC), as well as in an in vivo zebrafish (Danio rerio) embryo assay. The results suggest that ionic products of both MBG (Cu free) and MBG-5Cu materials promote angiogenesis. In vitro cell cultures show that the ionic dissolution products of these materials are not toxic and promote BAEC viability and migration. In addition, the in vivo assay indicates that both exposition and microinjection of zebrafish embryos with Cu free MBG material increase vessel number and thickness of the subintestinal venous plexus (SIVP), whereas assays using MBG-5Cu enhance this effect.The authors gratefully acknowledge the financial support provided by the Andalusian Ministry of Economy, Science and Innovation (Proyectos Excelencia Grants no. P10-CTS-6681 and no. P12-CTS-1507) and Spanish Ministry of Economy and Competitivity (BIO2014-56092-R). LBRS acknowledges the CONACYT-Mexico Fellowship PhD Program

Genetic analysis and functional characterization of factors affecting BM-derived myogenesis

Numerous common and severe human muscle disorders could benefit from stem cell therapy that would allow replacement of degenerating muscle. A recent upsurge of reports, claiming that readily accessible haematopoietic stem cells (HSCs) participate in muscle regeneration, raises hopes for their clinical application. However, the biology of this process and the proof of the ability of HSCs to be reprogrammed remain elusive. Using murine bone marrow (BM) cells, carrying different reporter cassettes controlled by elements of the muscle-specific Myf5, MLC3F and MCK promoters, we demonstrated that haematopoietic cells in co-culture with myoblasts express muscle-specific genes. In spite of this, these cells show limited regeneration of muscle in Pax7-/- mice and never give rise to myoblast clones. Correspondingly, the gene expression profiling of haematopoietic CD45+/Sca1+ cells revealed partial but extended myogenic reprogramming, despite the absence of key myogenic transcription factors such as Pax7 and MyoD. Indeed, BM transplantation and co-culture experiments, using BM cells from Pax7-/- or MyoD-/- mice, suggested that neither Pax7 nor MyoD are essential for the participation of haematopoietic cells in muscle regeneration, indicating that the Pax7 pathway is not active in these cells. In-vitro experiments with muscle cells from Pax7-/- /Myf5nlacZ/+ and Pax7-/-/MLC3F-nlacZ-E mice confirmed the tight association of Pax7 with the muscle-stem-cell characteristics. Additionally, the Pax7 ectopic expression in BM cells infused to them the ability to generate myogenic clones "and increased their in-vivo myogenic potential. Overall, our results demonstrate that BM-derived CD45+/Sca1+ cells, while undergoing myogenic specification and differentiation, cannot be considered muscle stem cells, and this latter distinction from the satellite cells is most probably due to the inactivity of the Pax7 pathway

Survival in patients with stage IV noncardia gastric cancer - the influence of DNA ploidy and Helicobacter Pyloriinfection

BACKGROUND: Palliative surgery followed by postoperative chemotherapy is a challenging approach in the treatment of stage IV gastric cancer yet patients must be carefully selected on the basis of likely clinical benefit. METHODS: The records of 218 patients with histological diagnosis of gastric adenocarcinoma who underwent palliative surgery followed by postoperative chemotherapy were retrospectively reviewed. Twelve potential prognostic variables including tumour DNA index and serum IgG anti- Helicobacter pylori (HP) antibodies were evaluated for their influence on overall survival by multivariate analysis. RESULTS: The median survival was 13.25 months [95% Confidence Interval (CI) 12.00, 14.50]. Three factors were found to have an independent effect on survival: performance status (PS) [PS 60–70 vs. 90–100 Hazard Ratio (HR) 1.676; CI 1.171-2.398, p = 0.005], liver metastases (HR 1.745; CI 1.318-2.310, p < 0.001), and DNA Index as assessed by Image cytometry (2.2-3.6 vs. >3.6 HR 3.059; CI 2.185-4.283, p < 0.001 and <2.2 vs. >3.6 HR; 4.207 CI 2.751-6.433 <0.001). HP infection had no statistically significant effect on survival by either univariate or multivariate analysis. CONCLUSION: Poor pre-treatment PS, the presence of liver metastasis and high DNA Index were identified factors associated with adverse survival outcome in patients with Stage IV gastric cancer treated with palliative gastrectomy and postoperative chemotherapy. HP infection had no influence on survival of these patients

Preparation and in vitro characterization of novel bioactive glass ceramic nanoparticles

SiO2-CaO-P2O5 ternary bioactive glass ceramic (BGC) nanoparticles with different compositions were prepared via a three-step sol-gel method. Polyethylene glycol was selected to be used as the surfactant to improve the dispersion of the nanoparticles. The morphology and composition of these BGC nanoparticles were observed by ESEM and EDX. All the BGC particles obtained in this method were about 20 nm in diameter. XRD analysis demonstrated that the different compositions can result in very different crystallinities for the BGC nanoparticles. Bioactivity tests in simulated body fluid solution (SBF), and degradability in phosphate buffer solution (PBS), were performed in vitro. SEM, EDX, and XRD were employed to monitor the surface variation of neat poly(L-lactic acid), PLLA, foam and PLLA/BGC porous scaffolds during incubation. The BGC nanoparticles with lower phosphorous and relative higher silicon content exhibited enhanced mineralization capability in SBF and a higher solubility in PBS medium. Such novel nanoparticles may have potential to be used in different biomedical applications, including tissue engineering or the orthopedic field.Contract grant sponsor: FCT; contract grant numbers: POCTI/FIS/61621/2004, SFRH/BPD/25828/2005, PTDC/QUI/69263/200

Network Forensic Investigation of Internal Misuse/Crime in Saudi Arabia: A Hacking Case

There are ad-hoc guidelines and a limited policy on computer incident response that does not include computer forensic preparation procedures (e.g. logging incidents). In addition, these guidelines do not consider the requirement of Islamic law for admissible evidence at an organisational level in Saudi Arabia. Network forensic investigation might breach the Saudi law if they follow ad-hoc or international digital forensic standards such as Association of Chief Police Officers (ACPO) guidelines. This might put the organisation in a costly situation when a malicious employee sues an Islamic court. This is because the law of Saudi Arabia is complying with Islamic (Al Sharia) law. Network forensic investigators should comprehend Islamic legal requirements for admissible evidence such as privacy of a suspect, integrity and availability of evidence. These legal requirements should be translated into information technology to conduct the processes of digital forensic. These processes include searching for, collecting, preserving and presenting electronic evidence in an Islamic court. Although insider abuse/crime have not been usually reported to the law enforcement in Saudi Arabia, a hacking case is provided and examined in order to highlight shortcomings for producing eevidence at an organisational level in Saudi Arabia. Furthermore, this case shows that there is a conflict between the technical (ad-hoc) process of collecting e-evidence which has been followed at an organisational level by network forensic investigators and the main principle of forensic procedure in Saudi Arabia. It also illustrates that there is no technical investigative standard for digital evidence. Moreover, this research addresses these issues by proposing a technical investigative standard for digital evidence. As a result of this standard, network forensic investigation is able to produce evidence with respect to the principles of forensic procedure in Saudi Arabia. Keywords: Internal threats, malicious insider, network forensic investigation, hacking, formal controls for digital forensics, technical controls for digital forensics, informal controls for digital forensics, forensic procedure in Saudi Arabi

Hypercalcemia in a patient with cholangiocarcinoma: a case report

<p>Abstract</p> <p>Background</p> <p>Humoral hypercalcemia of malignancy is rarely associated with cholangiocarcinoma (CC).</p> <p>Case report</p> <p>A 77-year-old man was admitted with confusion. Computer tomography showed a large multinodular mass in the right lobe of the liver and smaller lesions in the right lung. Liver histology confirmed the diagnosis of CC. Elevated calcium levels and suppressed intact parathyroid hormone in the absence of skeletal metastases or parathyroid gland pathology suggested the diagnosis of humoral hypercalcemia of malignancy (HHM). Treatment of hypercalcemia with saline infusion, loop diuretics, biphosphonate and calcitonin was effective in normalizing calcium levels and consciousness state within 48 hours, but a relapse occurred 4 weeks later and the patient succumbed to his disease.</p> <p>Conclusion</p> <p>Clinicians should be aware of this rare manifestation of CC as prompt and aggressive correction of hypercalcemia alleviates symptoms and improves patient's quality of life, despite the poor overall prognosis.</p

Design and characterization of a biodegradable double-layer scaffold aimed at periodontal tissue-engineering applications

First published: 1 September 2013The inefficacy of the currently used therapies in achieving the regeneration ad integrum of the periodontium stimulates the search for alternative approaches, such as tissue-engineering strategies. Therefore, the core objective of this study was to develop a biodegradable double-layer scaffold for periodontal tissue engineering. The design philosophy was based on a double-layered construct obtained from a blend of starch and poly-ε-caprolactone (30:70 wt%; SPCL). A SPCL fibre mesh functionalized with silanol groups to promote osteogenesis was combined with a SPCL solvent casting membrane aiming at acting as a barrier against the migration of gingival epithelium into the periodontal defect. Each layer of the double-layer scaffolds was characterized in terms of morphology, surface chemical composition, degradation behaviour and mechanical properties. Moreover, the behaviour of seeded/cultured canine adipose-derived stem cells (cASCs) was assessed. In general, the developed double-layered scaffolds demonstrated adequate degradation and mechanical behaviour for the target application. Furthermore, the biological assays revealed that both layers of the scaffold allow adhesion and proliferation of the seeded undifferentiated cASCs, and the incorporation of silanol groups into the fibre-mesh layer enhance the expression of a typical osteogenic marker. This study allowed an innovative construct to be developed, combining a three-dimensional (3D) scaffold with osteoconductive properties and with potential to assist periodontal regeneration, carrying new possible solutions to current clinical needs .The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013; under Grant Agreement No. REGPOT-CT2012-316331-POLARIS) and from the Portuguese Foundation for Science and Technology (FCT; Grant No, MIT/ECE/0047/2009). Joao Requicha acknowledges the FCT for his PhD scholarship ( Grant No. SFRH/BD/44143/2008)