The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony

A role for the Plasmodium falciparum cyclic GMP (cGMP)-dependent protein kinase (PfPKG) in gametogenesis in the malaria parasite was elucidated previously. In the present study we examined the role of PfPKG in the asexual blood-stage of the parasite life cycle, the stage that causes malaria pathology. A specific PKG inhibitor (compound 1, a trisubstituted pyrrole) prevented the progression of P. falciparum schizonts through to ring stages in erythrocyte invasion assays. Addition of compound 1 to ring-stage parasites allowed normal development up to 30 h postinvasion, and segmented schizonts were able to form. However, synchronized schizonts treated with compound 1 for ≥6 h became large and dysmorphic and were unable to rupture or liberate merozoites. To conclusively demonstrate that the effect of compound 1 on schizogony was due to its selective action on PfPKG, we utilized genetically manipulated P. falciparum parasites expressing a compound 1-insensitive PfPKG. The mutant parasites were able to complete schizogony in the presence of compound 1 but not in the presence of the broad-spectrum protein kinase inhibitor staurosporine. This shows that PfPKG is the primary target of compound 1 during schizogony and provides direct evidence of a role for PfPKG in this process. Discovery of essential roles for the P. falciparum PKG in both asexual and sexual development demonstrates that cGMP signaling is a key regulator of both of these crucial life cycle phases and defines this molecule as an exciting potential drug target for both therapeutic and transmission blocking action against malaria

Deafness–associated connexin 26 gene (GJB2) mutations in Iranian population

Mutations in the GJB2 gene at the DFNB1 locus on chromosome 13q12 are associated with autosomal recessive non syndromic hearing loss (ARNSHL) in many populations. A single mutation, at position 35 (35delG) accounts for approximately 30-63% of mutations in white populations with a carrier frequency of 1.5-2.5% in most European, North American and Mediterranean populations. In this study we have investigated the prevalence of the GJB2 gene mutations using direct sequencing in 43 presumed ARNSHL subjects from 34 families in an Iranian population. Eleven different genetic variants were identified. GJB2-related deafness mutations (35delG, 235delC, W24X, R184P and IVS1+1G>A) were found in 9 of 34 families (26.5%). The 35delG was the most common mutation found in 5 of 34 families (14.7%). We found one novel variant (–3517G>A) in the upstream region to the gene. The mutation frequency found in this study is lower than other ethnic groups with European ancestry, but it is indicating that mutation in GJB2 in Iranian population has contribution to ARNSHL. We have also developed a simple and accurate nested PCR assay to screen the 35delG mutation in 250 unrelated unaffected Iranian individual (controls). No 35delG heterozygous was found in the control population

Understanding information security culture: a survey in small and medium sized enterprises

Information security is a relevant fact for current organizations. There are factors inextricably linked to this issue, and one cannot talk about information security in an organization without addressing and understanding the information security culture of that institution. Maximizing the organizational culture within an organization will enable the safeguard of information security. For that, we need to understand which the inhibiting and the enabling factors are. This paper contributes to point out those factors by presenting the results of a survey concerning information security culture in small and medium sized enterprises (SMEs). We discuss the results in the light of related literature, and we identify future works aiming to enhance information security within organizations

On the global hydration kinetics of tricalcium silicate cement

We reconsider a number of measurements for the overall hydration kinetics of tricalcium silicate pastes having an initial water to cement weight ratio close to 0.5. We find that the time dependent ratio of hydrated and unhydrated silica mole numbers can be well characterized by two power-laws in time, $x/(1-x)\sim (t/t_x)^\psi$. For early times $t < t_x$ we find an `accelerated' hydration ($\psi = 5/2$) and for later times $t > t_x$ a `deaccelerated' behavior ($\psi = 1/2$). The crossover time is estimated as $t_x \approx 16 hours$. We interpret these results in terms of a global second order rate equation indicating that (a) hydrates catalyse the hydration process for $t<t_x$, (b) they inhibit further hydration for $t > t_x$ and (c) the value of the associated second order rate constant is of magnitude 6x10^{-7} - 7x10^{-6} liter mol^{-1} s^{-1}. We argue, by considering the hydration process actually being furnished as a diffusion limited precipitation that the exponents $\psi = 5/2$ and $\psi = 1/2$ directly indicate a preferentially `plate' like hydrate microstructure. This is essentially in agreement with experimental observations of cellular hydrate microstructures for this class of materials.Comment: RevTeX macros, 6 pages, 4 postscript figure

Lesbian and bisexual women's experiences of sexuality-based discrimination and their appearance concerns

Lesbian and bisexual women frequently experience sexuality-based discrimination, which is often based on others' judgements about their appearance. This short article aims to explore whether there is a relationship between lesbian and bisexual women's experiences of sexuality-based discrimination and their satisfaction with the way that they look. Findings from an online survey suggest that discrimination is negatively related to appearance satisfaction for lesbian women, but not for bisexual women. It is argued that this difference exists because lesbian appearance norms are more recognisable and distinctive than bisexual women's appearance norms

Scalar perturbation spectra from warm inflation

We present a numerical integration of the cosmological scalar perturbation equations in warm inflation. The initial conditions are provided by a discussion of the thermal fluctuations of an inflaton field and thermal radiation using a combination of thermal field theory and thermodynamics. The perturbation equations include the effects of a damping coefficient $\Gamma$ and a thermodynamic potential $V$. We give an analytic expression for the spectral index of scalar fluctuations in terms of a new slow-roll parameter constructed from $\Gamma$. A series of toy models, inspired by spontaneous symmetry breaking and a known form of the damping coefficient, lead to a spectrum with $n_s>1$ on large scales and $n_s<1$ on small scales.Comment: 12 pages, 5 figures, RevTeX 4, revised with extra figure

Postconviction Remedies, Retroactivity, and Montgomery v. Louisiana’s Other New Rule

The U.S. Supreme Court has turned its attention back to the law of habeas corpus, with a string of new decisions that emphasize the limited scope of federal habeas relief. But focusing one’s sights on only those decisions would overlook what has transpired at the Supreme Court in recent years in state habeas cases coming directly to the Supreme Court from the state postconviction courts. Montgomery v. Louisiana, in particular, shifted the division of power between the Supreme Court and state postconviction courts for questions conventionally considered to be questions of state law. Montgomery, on the surface, is a decision about retroactivity and th

A water-soluble core material for manufacturing hollow composite sections

This paper presents the development of a low-cost water-soluble core material, which is suitable for producing hollow composite structures via high pressure moulding processes, such as compression moulding and resin transfer moulding. The bulk material of the core is sodium chloride (NaCl), which is held together by a watersoluble trehalose binder. The composition of the core has been optimised to provide acceptable dissolution rates and mechanical properties for high volume structural composite applications. The compressive strength of the NaCl core was 57 MPa at ambient temperature, which reduced to 20 MPa when tested at 120 °C. The compressive strength at elevated temperature was approximately 4 times higher than for a water-soluble commercial benchmark and 33 times higher than a conventional structural closed-cell foam. The specific dissolution rate of the NaCl core was between 0.14 and 1.23 kg/(min·m2), depending on processing parameters and the coefficient of thermal expansion was approximately 43 × 10−6/K. A practical example has been presented to demonstrate how the removable core can be used to produce a representative hollow section of an integrally stiffened panel

On Entangled Multi-particle Systems in Bohmian Theory

Arguments are presented to show that in the case of entangled systems there are certain difficulties in implementing the usual Bohmian interpretation of the wave function in a straightforward manner. Specific examples are given.Comment: 7 page