Three-dimensional cell culture and tissue engineering in a T-CUP (tissue culture under perfusion)

The aim of this study was to develop and validate a simple and compact bioreactor system for perfusion cell seeding and culture through 3-dimensional porous scaffolds. The developed Tissue Culture Under Perfusion (T-CUP) bioreactor is based on the concept of controlled and confined alternating motion of scaffolds through a cell suspension or culture medium, as opposed to pumping of the fluid through the scaffolds. Via the T-CUP, articular chondrocytes and bone marrow stromal cells could be seeded into porous scaffolds of different compositions and architectures (chronOS, Hyaff-11, and Polyactive) at high efficiency (greater than 75%), uniformity (cells were well distributed throughout the scaffold pores), and viability (greater than 97%). Culture of articular chondrocytes seeded into 4-mm thick Polyactive scaffolds for 2 weeks in the T-CUP resulted in uniform deposition of cartilaginous matrix. Cultivation of freshly isolated human bone marrow nucleated cells seeded into ENGipore ceramic scaffolds for 19 days in the T-CUP resulted in stromal cell-populated constructs capable of inducing ectopic bone formation in nude mice. The T-CUP bioreactor represents an innovative approach to simple, efficient, and reliable 3D cell culture, and could be used either as a model to investigate mechanisms of tissue development or as a graft manufacturing system in the context of regenerative medicine

The role of epidermal growth factor-like module containing mucin-like hormone receptor 2 in human cancers.

G-protein coupled receptors (GPCRs) are among the most diverse and ubiquitous proteins in all of biology. The epidermal growth factor-seven span transmembrane (EGF-TM7) subfamily of adhesion GPCRs is a small subset whose members are mainly expressed on the surface of leukocytes. The EGF domains on the N-terminus add significant size to these receptors and they are considered to be among the largest members of the TM7 family. Although not all of their ligands or downstream targets have been identified, there is evidence implicating the EGF-TM7 family diverse processes such as cell adhesion, migration, inflammation, and autoimmune disease. Recent studies have identified expression of EGF-TM7 family members on human neoplasms including those of the thyroid, stomach, colon, and brain. Their presence on these tissues is not surprising given the ubiquity of GPCRs, but because their functional significance and pathways are not completely understood, they are of tremendous clinical and scientific interest. Current evidence suggests that expression of certain EGF-TM7 receptors is correlated with tumor grade, confers a more invasive phenotype, and increases the likelihood of metastatic disease. In this review, we will discuss the structure, function, and regulation of these receptors. We also describe the expression of these receptors in human cancers and explore their potential mechanistic significance

Public Liability: Questions Arising in Certain Farm and Ranch Recreation Enterprises.

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Laser Ablation for Gliomas

Laser interstitial thermal therapy (LITT) is a novel minimally invasive neurosurgical procedure in which laser light is delivered through a stereotactically positioned probe to an intracranial lesion for controlled thermal ablation of the pathological tissue. LITT is considered for patients who are poor candidates for open surgical resection due to (1) location of lesion (e.g., deep-seated or near critical structures), (2) history of intracranial interventions or medical comorbidities that increase surgical risk, or (3) lesion refractoriness to prior conventional therapies. The use of LITT was initially limited by concerns over off-target thermal damage; however, recent advances in magnetic resonance imaging-based thermal imaging have enabled real-time monitoring of tissue ablation dynamics, thereby improving its safety profile. Accordingly, the past two decades have seen a rapid expansion in the use of LITT for a variety of intracranial pathologies, including neoplasms, radiation necrosis, and epilepsy. This chapter focuses on the novel application of LITT to both newly diagnosed and recurrent glioblastoma multiforme (GBM). We first review the technological developments that enabled the safe use of LITT for GBM. We then review recent evidence regarding the indications, outcomes, and limitations of LITT as a novel adjuvant treatment for GBM

Immunocompetent murine models for the study of glioblastoma immunotherapy.

Glioblastoma remains a lethal diagnosis with a 5-year survival rate of less than 10%. (NEJM 352:987-96, 2005) Although immunotherapy-based approaches are capable of inducing detectable immune responses against tumor-specific antigens, improvements in clinical outcomes are modest, in no small part due to tumor-induced immunosuppressive mechanisms that promote immune escape and immuno-resistance. Immunotherapeutic strategies aimed at bolstering the immune response while neutralizing immunosuppression will play a critical role in improving treatment outcomes for glioblastoma patients. In vivo murine models of glioma provide an invaluable resource to achieving that end, and their use is an essential part of the preclinical workup for novel therapeutics that need to be tested in animal models prior to testing experimental therapies in patients. In this article, we review five contemporary immunocompetent mouse models, GL261 (C57BL/6), GL26 (C57BL/6) CT-2A (C57BL/6), SMA-560 (VM/Dk), and 4C8 (B6D2F1), each of which offer a suitable platform for testing novel immunotherapeutic approaches

Estimating population treatment effects from a survey sub-sample

We consider the problem of estimating an average treatment effect for a target population from a survey sub-sample. Our motivating example is generalizing a treatment effect estimated in a sub-sample of the National Comorbidity Survey Replication Adolescent Supplement to the population of U.S. adolescents. To address this problem, we evaluate easy-to-implement methods that account for both non-random treatment assignment and a non-random two-stage selection mechanism. We compare the performance of a Horvitz-Thompson estimator using inverse probability weighting (IPW) and two double robust estimators in a variety of scenarios. We demonstrate that the two double robust estimators generally outperform IPW in terms of mean-squared error even under misspecification of one of the treatment, selection, or outcome models. Moreover, the double robust estimators are easy to implement, providing an attractive alternative to IPW for applied epidemiologic researchers. We demonstrate how to apply these estimators to our motivating example

Single-kernel ionomic profiles are highly heritable indicators of genetic and environmental influences on elemental accumulation in maize grain (Zea mays)

Peer reviewedPublisher PD

Peculiar Multimodality on the Horizontal Branch of the Globular Cluster NGC 2808

We present distributions of colors of stars along the horizontal branch of the globular cluster NGC 2808, from Hubble Space Telescope WFPC2 imaging in B, V, and an ultraviolet filter (F218W). This cluster's HB is already known to be strongly bimodal, with approximately equal-sized HB populations widely separated in the color-magnitude diagram. Our images reveal a long blue tail with two gaps, for a total of four nearly distinct HB groups. These gaps are very narrow, corresponding to envelope-mass differences of only \sim 0.01 Msun. This remarkable multimodality may be a signature of mass-loss processes, subtle composition variations, or dynamical effects; we briefly summarize the possibilities. The existence of narrow gaps between distinct clumps on the HB presents a challenge for models that attempt to explain HB bimodality or other peculiar HB structures.Comment: LaTeX, including compressed figures. To appear in ApJL. Larger (851k) PostScript version, including high-quality figures, available from http://astro.berkeley.edu/~csosin/pub

An abrupt extinction in the Middle Permian (Capitanian) of the Boreal Realm (Spitsbergen) and its link to anoxia and acidification

The controversial Capitanian (Middle Permian, 262 Ma) extinction event is only known from equatorial latitudes, and consequently its global extent is poorly resolved. We demonstrate that there were two, severe extinctions amongst brachiopods in northern Boreal latitudes (Spitsbergen) in the Middle to Late Permian, separated by a recovery phase. New age dating of the Spitsbergen strata (belonging to the Kapp Starostin Formation), using strontium isotopes and d13C trends and comparison with better-dated sections in Greenland, suggests that the first crisis occurred in the Capitanian. This age assignment indicates that this Middle Permian extinction is manifested at higher latitudes. Redox proxies (pyrite framboids and trace metals) show that the Boreal crisis coincided with an intensification of oxygen depletion, implicating anoxia in the extinction scenario. The widespread and near-total loss of carbonates across the Boreal Realm also suggests a role for acidification in the crisis. The recovery interval saw the appearance of new brachiopod and bivalve taxa alongside survivors, and an increased mollusk dominance, resulting in an assemblage reminiscent of younger Mesozoic assemblages. The subsequent end-Permian mass extinction terminated this Late Permian radiation