Design and evaluation of effervescent floating tablets based on hydroxyethyl cellulose and sodium alginate using pentoxifylline as a model drug

The aim of this work was to design and evaluate effervescent floating gastro-retentive drug delivery matrix tablets with sustained-release behavior using a binary mixture of hydroxyethyl cellulose and sodium alginate. Pentoxifylline was used as a highly water-soluble, short half-life model drug with a high density. The floating capacity, swelling, and drug release behaviors of drug-loaded matrix tablets were evaluated in 0.1 N HCl (pH 1.2) at 37°C±0.5°C. Release data were analyzed by fitting the power law model of Korsmeyer–Peppas. The effect of different formulation variables was investigated, such as wet granulation, sodium bicarbonate gas-forming agent level, and tablet hardness properties. Statistical analysis was applied by paired sample t-test and one-way analysis of variance depending on the type of data to determine significant effect of different parameters. All prepared tablets through wet granulation showed acceptable physicochemical properties and their drug release profiles followed non-Fickian diffusion. They could float on the surface of dissolution medium and sustain drug release over 24 hours. Tablets prepared with 20% w/w sodium bicarbonate at 50–54 N hardness were promising with respect to their floating lag time, floating duration, swelling ability, and sustained drug release profile. Keywords: floating tablets, sodium alginate, pentoxifylline, dissolution, swelling, effervescen

Challenges in identifying cancer genes by analysis of exome sequencing data.

Massively parallel sequencing has permitted an unprecedented examination of the cancer exome, leading to predictions that all genes important to cancer will soon be identified by genetic analysis of tumours. To examine this potential, here we evaluate the ability of state-of-the-art sequence analysis methods to specifically recover known cancer genes. While some cancer genes are identified by analysis of recurrence, spatial clustering or predicted impact of somatic mutations, many remain undetected due to lack of power to discriminate driver mutations from the background mutational load (13-60% recall of cancer genes impacted by somatic single-nucleotide variants, depending on the method). Cancer genes not detected by mutation recurrence also tend to be missed by all types of exome analysis. Nonetheless, these genes are implicated by other experiments such as functional genetic screens and expression profiling. These challenges are only partially addressed by increasing sample size and will likely hold even as greater numbers of tumours are analysed

Sexual reproduction of human fungal pathogens

We review here recent advances in our understanding of sexual reproduction in fungal pathogens that commonly infect humans, including Candida albicans, Cryptococcus neoformans/gattii, and Aspergillus fumigatus. Where appropriate or relevant, we introduce findings on other species associated with human infections. In particular, we focus on rapid advances involving genetic, genomic, and population genetic approaches that have reshaped our view of how fungal pathogens evolve. Rather than being asexual, mitotic, and largely clonal, as was thought to be prevalent as recently as a decade ago, we now appreciate that the vast majority of pathogenic fungi have retained extant sexual, or parasexual, cycles. In some examples, sexual and parasexual unions of pathogenic fungi involve closely related individuals, generating diversity in the population but with more restricted recombination than expected from fertile, sexual, outcrossing and recombining populations. In other cases, species and isolates participate in global outcrossing populations with the capacity for considerable levels of gene flow. These findings illustrate general principles of eukaryotic pathogen emergence with relevance for other fungi, parasitic eukaryotic pathogens, and both unicellular and multicellular eukaryotic organisms

Matter sources for a Null Big Bang

We consider the properties of stress-energy tensors compatible with a Null Big Bang, i.e., cosmological evolution starting from a Killing horizon rather than a singularity. For Kantowski-Sachs cosmologies, it is shown that if matter satisfies the Null Energy Condition (NEC), then (i) regular cosmological evolution can only start from a Killing horizon, (ii) matter is absent at the horizon, and (iii) matter can only appear in the cosmological region due to interaction with vacuum. The latter is understood phenomenologically as a fluid whose stress tensor is insensitive to boosts in a particular direction. We also argue that matter is absent in a static region beyond the horizon. All this generalizes the observations recently obtained for a mixture of dust and a vacuum fluid. If, however, we admit the existence of phantom matter, its certain special kinds (with the parameter $w \leq -3$) are consistent with a Null Big Bang without interaction with vacuum (or without vacuum fluid at all). Then in the static region there is matter with $w\geq -1/3$. Alternatively, the evolution can begin from a horizon in an infinitely remote past, leading to a scenario combining the features of a Null Big Bang and an emergent universe.Comment: 5 two-column pages, revtex4, no figures. One reference corrected. Final version accepted for publication in Class. Quantum Gra

ESTUDO LONGITUDINAL DE FATORES QUE AFETAM O RISCO DE FRATURA POR ESTRESSE EM DUAS POPULAÇÕES DE COLEGIAIS DO SEXO FEMININO

Objetivos: As fraturas por estresse causam significante morbidade em mulheres. Diferenças no nível de atividades, valores hormonais e densidade mineral óssea (BMD) afetam diferentemente as taxas de fraturas por estresse. Os autores hipotetizaram que mulheres de um Colégio militar terão maior nível de atividade do que mulheres em colégios com um ambiente mais flexível, que correlacionará com mudanças nos valores hormonais, menor (BMD) e mais fraturas por estresse. Método: Nesse estudo prospectivo comparativo, 63 mulheres de duas Instituições (The Citadel: The Military College Of South Carolina And The College Of Cherleston) relataram detalhadamente suas atividades, dieta e lesões através de um questionário e tiveram sua BMB e os valores hormonais séricos medidos num intervalo de 06 meses, por um período de 2 anos; 38 sujeitos completaram o estudo. A análise estatística examinou diferenças e mudanças ao longo do tempo entre as duas amostras.Resultados: Uma fratura por estresse ocorreu em cada Instituição. As mulheres do Citadel tiveram maiores níveis de atividade, que as mulheres do College of Charleston no longo do estudo. As mulheres do Citadel tiveram menor nível de hormônio folículo estimulante, maior 17 Beta-Estradiol aos 24 meses e maior BMD na extremidade proximal femoral aos 18 meses da investigação (p< 0,05). Conclusões: Os valores séricos hormonais podem ser um indicador mais sensível de resposta ao nível da atividade física que o BMD dentro da amostra e duração deste estudo. Outros estudos são necessários para definir esta complexa interrelação. LONGITUDINAL STUDY OF FACTORS AFFECTING STRESS FRACTURE RISK IN TWO DISTINCT COLLEGE FEMALE POPULATIONS Abstract Objectives: Stress fractures cause significant morbidity in females. Differences in activity levels, hormone values, and bone mineral density (BMD) affect different rates of stress fracture. The authors hypothesized that females at a military college will have greater activity levels than females in a flexible college environment, which will correlate with greater changes in hormone values, lower BMD, and more stress fractures. Methods: In this prospective comparative study 63 females from two institutions (The Citadel: The Military College of South Carolina and the College of Charleston) self-reported on a detailed activity, diet, and injury questionnaire and had BMD and serum hormone values measured at 6- month intervals for a two year period; 38 completed the study. Statistical analysis was designed to examine differences and changes over time between the two samples. Results: One stress fracture occurred in each institution. Citadel females had higher activity levels than females at the College of Charleston throughout the study. Citadel females had lower follicle stimulating hormone levels at 24 months, greater 17 beta-estradiol at 24 months, and greater proximal femoral BMD at eighteen months (

Cluster Alignments and Ellipticities in LCDM Cosmology

The ellipticities and alignments of clusters of galaxies, and their evolution with redshift, are examined in the context of a Lambda-dominated cold dark matter cosmology. We use a large-scale, high-resolution N-body simulation to model the matter distribution in a light cone containing ~10^6 clusters out to redshifts of z=3. Cluster ellipticities are determined as a function of mass, radius, and redshift, both in 3D and in projection. We find strong cluster ellipticities: the mean ellipticity increases with redshift from 0.3 at z=0 to 0.5 at z=3, for both 3D and 2D ellipticities; the evolution is well-fit by e=0.33+0.05z. The ellipticities increase with cluster mass and with cluster radius; the main cluster body is more elliptical than the cluster cores, but the increase of ellipticities with redshift is preserved. Using the fitted cluster ellipsoids, we determine the alignment of clusters as a function of their separation. We find strong alignment of clusters for separations <100 Mpc/h; the alignment increases with decreasing separation and with increasing redshift. The evolution of clusters from highly aligned and elongated systems at early times to lower alignment and elongation at present reflects the hierarchical and filamentary nature of structure formation. These measures of cluster ellipticity and alignment will provide a new test of the current cosmological model when compared with upcoming cluster surveys.Comment: 29 pages including 13 figures, to appear in ApJ Jan. 2005 (corrected typos, added reference

A conceptual design study of the reusable reentry satellite

Experimentation leading to an understanding of life processes under reduced and extremely low gravitational forces will profoundly contribute to the success of future space missions involving humans. In addition to research on gravitational biology, research on the effects of cosmic radiation and the interruption and change of circadian rhythms on life systems is also of prime importance. Research in space, however, is currently viewed by biological scientists as an arena that is essential, yet largely inaccessible to them for their experimentation. To fulfill this need, a project and spacecraft system described as the Reusuable Reentry Satellite or Lifesat has been proposed by NASA