Dynamics and pattern formation in invasive tumor growth

In this work, we study the in-vitro dynamics of the most malignant form of the primary brain tumor: Glioblastoma Multiforme. Typically, the growing tumor consists of the inner dense proliferating zone and the outer less dense invasive region. Experiments with different types of cells show qualitatively different behavior. Wild-type cells invade a spherically symmetric manner, but mutant cells are organized in tenuous branches. We formulate a model for this sort of growth using two coupled reaction-diffusion equations for the cell and nutrient concentrations. When the ratio of the nutrient and cell diffusion coefficients exceeds some critical value, the plane propagating front becomes unstable with respect to transversal perturbations. The instability threshold and the full phase-plane diagram in the parameter space are determined. The results are in a good agreement with experimental findings for the two types of cells.Comment: 4 pages, 4 figure

Excellent diagnostic characteristics for ultrafast gene profiling of DEFA1-IL1B-LTF in detection of prosthetic joint infections

The timely and exact diagnosis of prosthetic joint infection (PJI) is crucial for surgical decision-making. Intraoperatively, delivery of the result within an hour is required. Alpha-defensin lateral immunoassay of joint fluid (JF) is precise for the intraoperative exclusion of PJI; however, for patients with a limited amount of JF and/or in cases where the JF is bloody, this test is unhelpful. Important information is hidden in periprosthetic tissues that may much better reflect the current status of implant pathology. We therefore investigated the utility of the gene expression patterns of 12 candidate genes (TLR1, -2, -4, -6, and 10, DEFA1, LTF, IL1B, BPI, CRP, IFNG, and DEFB4A) previously associated with infection for detection of PJI in periprosthetic tissues of patients with total joint arthroplasty (TJA) (n = 76) reoperated for PJI (n = 38) or aseptic failure (n = 38), using the ultrafast quantitative reverse transcription-PCR (RT-PCR) Xxpress system (BJS Biotechnologies Ltd.). Advanced data-mining algorithms were applied for data analysis. For PJI, we detected elevated mRNA expression levels of DEFA1 (P < 0.0001), IL1B (P < 0.0001), LTF (P < 0.0001), TLR1 (P = 0.02), and BPI (P = 0.01) in comparison to those in tissues from aseptic cases. A feature selection algorithm revealed that the DEFA1-IL1B-LTF pattern was the most appropriate for detection/exclusion of PJI, achieving 94.5% sensitivity and 95.7% specificity, with likelihood ratios (LRs) for positive and negative results of 16.3 and 0.06, respectively. Taken together, the results show that DEFA1-IL1B-LTF gene expression detection by use of ultrafast qRT-PCR linked to an electronic calculator allows detection of patients with a high probability of PJI within 45 min after sampling. Further testing on a larger cohort of patients is needed.Web of Science5592697268

Coverage-dependent adsorption sites in the K/Ru(0001) system: a low-energy electron-diffraction analysis

The two ordered phases p(2 × 2) at a coverage θ = 0.25 and (√3 × √3)R30° at θ = 0.33 of potassium adsorbed on Ru(0001) were analyzed by use of low-energy electron-diffraction (LEED). In the (√3 × √3)R30° phase, the K atoms occupy threefold hcp sites, while in the p(2 × 2) phase the fcc site is favoured. In both phases, the K hard-sphere radii are nearly the same and close to the covalent Pauling radius

Polymer multilayer tattooing for enhanced DNA vaccination

DNA vaccines have many potential benefits but have failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These ‘multilayer tattoo’ DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.Howard Hughes Medical Institute (Investigator)Ragon Institute of MGH, MIT, and HarvardNational Institutes of Health (U.S.) (NIH AI095109)United States. Dept. of Defense. Institute for Soldier Nanotechnologies (contract W911NF-07-D-0004)United States. Dept. of Defense. Institute for Soldier Nanotechnologies (contract W911NF-07-0004

Composite Dissolving Microneedles for Coordinated Control of Antigen and Adjuvant Delivery Kinetics in Transcutaneous Vaccination

Transcutaneous administration has the potential to improve therapeutics delivery, providing an approach that is safer and more convenient than traditional alternatives, while offering the opportunity for improved therapeutic efficacy through sustained/controlled drug release. To this end, a microneedle materials platform is demonstrated for rapid implantation of controlled-release polymer depots into the cutaneous tissue. Arrays of microneedles composed of drug-loaded poly(lactide-co-glycolide) (PLGA) microparticles or solid PLGA tips are prepared with a supporting and rapidly water-soluble poly(acrylic acid) (PAA) matrix. Upon application of microneedle patches to the skin of mice, the microneedles perforate the stratum corneum and epidermis. Penetration of the outer skin layers is followed by rapid dissolution of the PAA binder on contact with the interstitial fluid of the epidermis, implanting the microparticles or solid polymer microneedles in the tissue, which are retained following patch removal. These polymer depots remain in the skin for weeks following application and sustain the release of encapsulated cargos for systemic delivery. To show the utility of this approach the ability of these composite microneedle arrays to deliver a subunit vaccine formulation is demonstrated. In comparison to traditional needle-based vaccination, microneedle delivery gives improved cellular immunity and equivalent generation of serum antibodies, suggesting the potential of this approach for vaccine delivery. However, the flexibility of this system should allow for improved therapeutic delivery in a variety of diverse contexts.Massachusetts Institute of Technology. Ragon Institute of MGH, MIT and HarvardNational Institutes of Health (U.S.) (Award AI095109)United States. Army Research Office (Contract W911NF-07-D-0004

Simplicity of extremal eigenvalues of the Klein-Gordon equation

We consider the spectral problem associated with the Klein-Gordon equation for unbounded electric potentials. If the spectrum of this problem is contained in two disjoint real intervals and the two inner boundary points are eigenvalues, we show that these extremal eigenvalues are simple and possess strictly positive eigenfunctions. Examples of electric potentials satisfying these assumptions are given

Transformation Pathways of Silica under High Pressure

Concurrent molecular dynamics simulations and ab initio calculations show that densification of silica under pressure follows a ubiquitous two-stage mechanism. First, anions form a close-packed sub-lattice, governed by the strong repulsion between them. Next, cations redistribute onto the interstices. In cristobalite silica, the first stage is manifest by the formation of a metastable phase, which was observed experimentally a decade ago, but never indexed due to ambiguous diffraction patterns. Our simulations conclusively reveal its structure and its role in the densification of silica.Comment: 14 pages, 4 figure

Multilingual assessment of early child development: Analyses from repeated observations of children in Kenya.

In many low- and middle-income countries, young children learn a mother tongue or indigenous language at home before entering the formal education system where they will need to understand and speak a countrys official language(s). Thus, assessments of children before school age, conducted in a nations official language, may not fully reflect a childs development, underscoring the importance of test translation and adaptation. To examine differences in vocabulary development by language of assessment, we adapted and validated instruments to measure developmental outcomes, including expressive and receptive vocabulary. We assessed 505 2-to-6-year-old children in rural communities in Western Kenya with comparable vocabulary tests in three languages: Luo (the local language or mother tongue), Swahili, and English (official languages) at two time points, 5-6&nbsp;weeks apart, between September 2015 and October 2016. Younger children responded to the expressive vocabulary measure exclusively in Luo (44%-59% of 2-to-4-year-olds) much more frequently than did older children (20%-21% of 5-to-6-year-olds). Baseline receptive vocabulary scores in Luo (β&nbsp;=&nbsp;0.26, SE&nbsp;=&nbsp;0.05, p&nbsp;&lt;&nbsp;0.001) and Swahili (β&nbsp;=&nbsp;0.10, SE&nbsp;=&nbsp;0.05, p&nbsp;=&nbsp;0.032) were strongly associated with receptive vocabulary in English at follow-up, even after controlling for English vocabulary at baseline. Parental Luo literacy at baseline (β&nbsp;=&nbsp;0.11, SE&nbsp;=&nbsp;0.05, p&nbsp;=&nbsp;0.045) was associated with child English vocabulary at follow-up, while parental English literacy at baseline was not. Our findings suggest that multilingual testing is essential to understanding the developmental environment and cognitive growth of multilingual children

The acquisition of Sign Language: The impact of phonetic complexity on phonology

Research into the effect of phonetic complexity on phonological acquisition has a long history in spoken languages. This paper considers the effect of phonetics on phonological development in a signed language. We report on an experiment in which nonword-repetition methodology was adapted so as to examine in a systematic way how phonetic complexity in two phonological parameters of signed languages — handshape and movement — affects the perception and articulation of signs. Ninety-one Deaf children aged 3–11 acquiring British Sign Language (BSL) and 46 hearing nonsigners aged 6–11 repeated a set of 40 nonsense signs. For Deaf children, repetition accuracy improved with age, correlated with wider BSL abilities, and was lowest for signs that were phonetically complex. Repetition accuracy was correlated with fine motor skills for the youngest children. Despite their lower repetition accuracy, the hearing group were similarly affected by phonetic complexity, suggesting that common visual and motoric factors are at play when processing linguistic information in the visuo-gestural modality