Neurotransmitter Specific, Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility.

Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs) with two different geometries (sphere and rod) and quantum dots (QDs) with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA), and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach

Deformed triangular lattice antiferromagnets in a magnetic field: role of spatial anisotropy and Dzyaloshinskii-Moriya interactions

Recent experiments on the anisotropic spin-1/2 triangular antiferromagnet Cs_2CuBr_4 have revealed a remarkably rich phase diagram in applied magnetic fields, consisting of an unexpectedly large number of ordered phases. Motivated by this finding, we study the role of spatial anisotropy, Dzyaloshinskii-Moriya interactions, and quantum fluctuations on the magnetization process of a triangular antiferromagnet, coming from the semiclassical limit. The richness of the problem stems from two key facts: 1) the classical isotropic model exhibits a large accidental ground state degeneracy, and 2) these three ingredients compete with one another and split this degeneracy in opposing ways. Using a variety of complementary approaches, including extensive Monte Carlo numerics, spin-wave theory, and an analysis of Bose-Einstein condensation of magnons at high fields, we find that their interplay gives rise to a complex phase diagram consisting of numerous incommensurate and commensurate phases. Our results shed light on the observed phase diagram for Cs_2CuBr_4 and suggest a number of future theoretical and experimental directions that will be useful for obtaining a complete understanding of this material's interesting phenomenology.Comment: 22 pages, 16 figures; Submission errors correcte

Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.

BackgroundProstate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study.MethodsProstaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice.ResultsProstate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells.ConclusionHuman prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells

Ossification of the Posterior Longitudinal Ligament: Surgical Approaches and Associated Complications.

Ossification of the posterior longitudinal ligament (OPLL) is a rare but potentially devastating cause of degenerative cervical myelopathy (DCM). Decompressive surgery is the standard of care for OPLL and can be achieved through anterior, posterior, or combined approaches to the cervical spine. Surgical correction of OPLL via any approach is associated with higher rates of complications and the presence of OPLL is considered a significant risk factor for perioperative complications in DCM surgeries. Potential complications include dural tear (DT) and subsequent cerebrospinal fluid leak, C5 palsy, hematoma, hardware failure, surgical site infections, and other neurological deficits. Anterior approaches are technically more demanding and associated with higher rates of DT but offer greater access to ventral OPLL pathology. Posterior approaches are associated with lower rates of complications but may allow for continued disease progression. Therefore, the decision to pursue either an anterior or posterior approach to surgical decompression may be critically influenced by complications associated with each procedure. The authors critically review anterior and posterior approaches to surgical decompression of OPLL with particular focus on the complications associated with each approach. We also review the recent work in developing new surgical treatments for OPLL that aim to reduce complication incidence

Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

IntroductionDisruption of metabolic function is a recognized feature of late onset Alzheimer's disease (LOAD). We sought to determine whether similar metabolic pathways are implicated in adults with Down syndrome (DS) who have increased risk for Alzheimer's disease (AD).MethodsWe examined peripheral blood from 292 participants with DS who completed baseline assessments in the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) using untargeted mass spectrometry (MS). Our sample included 38 individuals who met consensus criteria for AD (DS-AD), 43 who met criteria for mild cognitive impairment (DS-MCI), and 211 who were cognitively unaffected and stable (CS).ResultsWe measured relative abundance of 8,805 features using MS and 180 putative metabolites were differentially expressed (DE) among the groups at false discovery rate-corrected q< 0.05. From the DE features, a nine-feature classifier model classified the CS and DS-AD groups with receiver operating characteristic area under the curve (ROC AUC) of 0.86 and a two-feature model classified the DS-MCI and DS-AD groups with ROC AUC of 0.88. Metabolite set enrichment analysis across the three groups suggested alterations in fatty acid and carbohydrate metabolism.DiscussionOur results reveal metabolic alterations in DS-AD that are similar to those seen in LOAD. The pattern of results in this cross-sectional DS cohort suggests a dynamic time course of metabolic dysregulation which evolves with clinical progression from non-demented, to MCI, to AD. Metabolomic markers may be useful for staging progression of DS-AD

Spinal Cord Stimulation in the 21st Century — Reviewing Innovation in Neuromodulation

INTRODUCTION Low back pain (LBP) is a pervasive problem impacting health systems across the world. In the United States, chronic LBP impacts up to 40% of Americans and results in excessive financial strain on the healthcare budget, estimated at up to $100 billion annually.1 Furthermore, treatment results are often disappointing, with the traditional pathway of conservative measures, narcotic pain medication, and surgical decompression and/or fusion leading to both patient and provider frustration, complications, and diminished patient productivity and quality of life. This has naturally led to questions from policymakers regarding the utility of healthcare dollars spent on back pain. In this milieu, a variety of neuromodulation techniques have found a niche in the management of this patient population, with indications commonly quoted including failed back surgery syndrome (FBSS), chronic neuropathic pain, and complex regional pain syndrome (CRPS), among others.1,2 From its inception on the basis of Melzak and Wall’s gate theory³, to its first human trial in the 1960s,⁴ and to the modern era, spinal cord stimulation has undergone a series of innovations that have expanded indications and improved patient outcomes. The goal of this study is to summarize the most important clinical trials involving both traditional SCS and newer stimulation paradigms to provide an overview of the current state of affairs of this rapidly-growing field

An Assemblage of Lava Flow Features on Mercury

In contrast to other terrestrial planets, Mercury does not possess a great variety of volcanic features, its history of volcanism instead largely manifest by expansive smooth plains. However, a set of landforms at high northern latitudes on Mercury resembles surface flow features documented on Earth, the Moon, Mars, and Venus. The most striking of such landforms are broad channels that host streamlined islands and that cut through the surrounding intercrater plains. Together with narrower, more sinuous channels, coalesced depressions, evidence for local flooding of intercrater plains by lavas, and a first-order analysis of lava flow rates, the broad channels define an assemblage of flow features formed by the overland flow of, and erosion by, voluminous, high-temperature, low-viscosity lavas. This interpretation is consistent with compositional data suggesting that substantial portions of Mercury's crust are composed of magnesian, iron-poor lithologies. Moreover, the proximity of this partially flooded assemblage to extensive volcanic plains raises the possibility that the formation of these flow features may preface total inundation of an area by lavas emplaced in a flood mode and that they escaped complete burial only due to a waning magmatic supply. Finally, that these broad channels on Mercury are volcanic in nature yet resemble outflow channels on Mars, which are commonly attributed to catastrophic water floods, implies that aqueous activity is not a prerequisite for the formation of such distinctive landforms on any planetary body

Deformation Associated with Ghost Craters and Basins in Volcanic Smooth Plains on Mercury: Strain Analysis and Implications for Plains Evolution

Since its insertion into orbit about Mercury in March 2011, the MESSENGER spacecraft has imaged most previously unseen regions of the planet in unprecedented detail, revealing extensive regions of contiguous smooth plains at high northern latitudes and surrounding the Caloris basin. These smooth plains, thought to be emplaced by flood volcanism, are populated with several hundred ghost craters and basins, nearly to completely buried impact features having rims for which the surface expressions are now primarily rings of deformational landforms. Associated with some ghost craters are interior groups of graben displaying mostly polygonal patterns. The origin of these graben is not yet fully understood, but comparison with numerical models suggests that the majority of such features are the result of stresses from local thermal contraction. In this paper, we highlight a previously unreported category of ghost craters, quantify extensional strains across graben-bearing ghost craters, and make use of graben geometries to gain insights into the subsurface geology of smooth plains areas. In particular, the style and mechanisms of graben development imply that flooding of impact craters and basins led to substantial pooling of lavas, to thicknesses of ∼1.5 km. In addition, surface strains derived from groups of graben are generally in agreement with theoretically and numerically derived strains for thermal contraction

Organization of Multinational Activities and Ownership Structure

We develop a model in which multinational investors decide about the modes of organization, the locations of production, and the markets to be served. Foreign investments are driven by market-seeking and cost-reducing motives. We further assume that investors face costs of control that vary among sectors and increase in distance. The results show that (i) production intensive sectors are more likely to operate a foreign business independent of the investment motive, (ii) that distance may have a non-monotonous effect on the likelihood of horizontal investments, and (iii) that globalization, if understood as reducing distance, leads to more integration

Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma

BACKGROUND: Conventional cancer therapy including surgery, radiation, and chemotherapy often are physically debilitating and largely ineffective in previously treated patients with recurrent head and neck squamous cell carcinoma (SCC). A natural photochemical, hypericin, could be a less invasive method for laser photodynamic therapy (PDT) of these recurrent head and neck malignancies. Hypericin has powerful photo-oxidizing ability, tumor localization properties, and fluorescent imaging capabilities as well as minimal dark toxicity. The current study defined hypericin PDT in vitro with human SCC cells before the cells were grown as tumor transplants in nude mice and tested as a model for hypericin induced tumor fluorescence and PDT via laser fiberoptics. METHODS: SNU squamous carcinoma cells were grown in tissue culture, detached from monolayers with trypsin, and incubated with 0.1 μg to 10 μg/ml of hypericin before exposure to laser light at 514, 550, or 593 nm to define optimal dose, time, and wavelength for PDT of tumor cells. The SCC cells also were injected subcutaneously in nude mice and grown for 6–8 weeks to form tumors before hypericin injection and insertion of fiberoptics from a KTP532 surgical laser to assess the feasibility of this operating room instrument in stimulating fluorescence and PDT of tumors. RESULTS: In vitro testing revealed a hypericin dose of 0.2–0.5 μg/ml was needed for PDT of the SCC cells with an optimal tumoricidal response seen at the 593 nm light absorption maximum. In vivo tumor retention of injected hypericin was seen for 7 to10 days using KTP532 laser induced fluorescence and biweekly PDT via laser fiberoptics led to regression of SCC tumor transplants under 0.4 cm(2 )diameter, but resulted in progression of larger size tumors in the nude mice. CONCLUSION: In this preclinical study, hypericin was tested for 514–593 nm dye laser PDT of human SCC cells in vitro and for KTP532 surgical laser targeting of SCC tumors in mice. The results suggest hypericin is a potent tumor imaging agent using this surgical laser that may prove useful in defining tumor margins and possibly in sterilizing post-resection margins. Deeply penetrating pulsed infrared laser emissions will be needed for PDT of larger and more inaccessible tumors