Intracerebral Implantation of Ionic Synthetic Hydrogels: Effect of Polar Substrata on Astrocytosis and Axons

In previous studies, hyperporous synthetic hydrogels of poly(glyceryl methacrylate) or p(GMA), containing bioadhesive substrates of collagen, were implanted into rat cerebral tissue in order to provide systems of oriented guidance channels for directing the growth of the scar and axons /28/. In the present study, ionic p(GMA)- collagen hydrogels containing polar chemical groups, either basic amino groups or acidic carboxyl groups, were evaluated for their tolerance and their effects on the brain scarring response and axonal reactivity after long-term implantation in the cerebral cortex. In all animals, the implants were well tolerated. Although both types of gels influenced the astroglial reaction near the bioimplant, hydrogels carrying carboxyl groups had the strongest influence on the elongation, the direction and the organization of astrocytic processes so that a glial matrix could form in regions of the gel. Extracellular material (e.g. reticulin) was also deposited into the gels carrying carboxyl groups. Although cortical nerve fibers .in the surrounding tissue showed a regenerative response, extending onto or into the matrices, this behavior seemed to depend more on the organization of the .astrocytic scar imposed by the gel than on the type of gel. We conclude that matrices carrying negatively charged groups influence favorably the astrocytosis and the deposition of connective tissue, and that this approach represents a new avenue in attempting to modulate the brain scar formation

Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.

Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation

Resistless electron beam lithography process for the fabrication of sub-50 nm silicide structures

We report on a study of the fabrication of submicron silicide structures with a resistless lithography technique. Several different metals can be used as a basis for producing silicide using this method; in this work, results will be discussed for both platinum and nickel silicide. The feasibility of producing nanostructures using polycrystalline silicon as a base growth layer for metal–oxide– semiconductor, and other device applications have also been demonstrated. Threshold doses for this method for submicron lines (<50 nm) and square areas were obtained in order to establish a framework for the fabrication of more complex devices. Preliminary electrical measurements were carried out which indicate that the resistivity of the silicide is 45 [mu omega] cm, and that the barrier height of the silicide/(high resistivity silicon) interface is 0.56 eV

Crystal plasticity as an indicator of the viscous-brittle transition in magmas

Understanding the flow of multi-phase (melt, crystals and bubbles) magmas is of great importance for interpreting eruption dynamics. Here we report the first observation of crystal plasticity, identified using electron backscatter diffraction, in plagioclase in andesite dome lavas from Volcán de Colima, Mexico. The same lavas, deformed experimentally at volcanic conduit temperature and load conditions, exhibit a further, systematic plastic response in the crystalline fraction, observable as a lattice misorientation. At higher stress, and higher crystal fraction, the amount of strain accommodated by crystal plasticity is larger. Crystal plastic distortion is highest in the intact segments of broken crystals, which have exceeded their plastic limit. We infer that crystal plasticity precludes failure and can punctuate the viscous-brittle transition in crystal-bearing magmas at certain shallow magmatic conditions. Since crystal plasticity varies systematically with imposed conditions, this raises the possibility that it may be used as a strain marker in well-constrained systems

Method for fabricating submicron silicide structures on silicon using a resistless electron beam lithography process

Abstract : A novel resistless lithography process using a conventional electron beam system is presented. Metallic lines with widths of less than 50 nm were produced on silicon substrates. The process is based on localized heating with a focused electron beam of thin platinum layers deposited on silicon. It is demonstrated that silicide formation occurs at the Pt-Si interface. By using a dilute solution of aqua regia, it is possible to obtain a sufficient difference in etch rates between exposed and unexposed regions of the platinum thin film to selectively remove only the unexposed areas

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb

Absolute Paleointensity Study of Miocene Tiva Canyon Tuff, Yucca Mountain, Nevada: Role of Fine‐Particle Grain‐Size Variations

Fine‐grained, Ti‐poor titanomagnetite in the ~12.7 Ma Tiva Canyon (TC) Tuff systematically increases in grain size from superparamagnetic (SP) at the flow base to single domain (SD) at a few meters height. This allows us to examine the role of grain‐size variation on paleointensity, within the transition from SP to stable SD. We present magnetic properties from two previously unreported sections of the TC Tuff, as well as Thellier‐type paleointensity estimates from the lowermost ~7.0 m of the flow. Magnetic hysteresis, frequency‐dependent susceptibility, and thermomagnetic data show that sample grain‐size distribution is dominated by SP in the lower ~3.6 m, transitioning upwards to mostly stable SD. Paleointensity results are closely tied to stratigraphic height and to magnetic properties linked to domain state. SD samples have consistent absolute paleointensity values of 28.5 ± 1.94 μT (VADM of 51.3 ZAm2) and behaved ideally during paleointensity experiments. The samples including a significant SP fraction have consistently higher paleointensities and less ideal behavior but would likely pass many traditional quality‐control tests. We interpret the SD remanence to be a primary thermal remanent magnetization but discuss the possibility of a partial thermal‐chemical remanent magnetization if microcrystal growth continued at T \u3c Tc and/or the section is affected by post‐emplacement vapor‐phase alteration. The link between paleointensity and domain state is stronger than correlations with water content or other evidence of alteration and suggests that the presence of a significant SP population may adversely impact paleointensity results, even in the presence of a stable SD fraction

Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity

Dendritic cells (DCs) play a critical role in orchestrating adaptive immune responses due to their unique ability to initiate T cell responses and direct their differentiation into effector lineages. Classical DCs have been divided into two subsets, cDC1 and cDC2, based on phenotypic markers and their distinct abilities to prime CD8 and CD4 T cells. While the transcriptional regulation of the cDC1 subset has been well characterized, cDC2 development and function remain poorly understood. By combining transcriptional and chromatin analyses with genetic reporter expression, we identified two principal cDC2 lineages defined by distinct developmental pathways and transcriptional regulators, including T-bet and RORgt, two key transcription factors known to define innate and adaptive lymphocyte subsets. These novel cDC2 lineages were characterized by distinct metabolic and functional programs. Extending our findings to humans revealed conserved DC heterogeneity and the presence of the newly defined cDC2 subsets in human cancer