Room temperature negative differential resistance of a monolayer molecular rotor device

An electrically driven molecular rotor device comprised of a monolayer of redox-active ligated copper compounds sandwiched between a gold electrode and a highly doped P+Si substrate was fabricated. Current-voltage spectroscopy revealed a temperature-dependent negative differential resistance (NDR) associated with the device. Time-dependent density functional theory suggests the source of the observed NDR to be redox-induced ligand rotation around the copper metal center, an explanation consistent with the proposed energy diagram of the device. An observed temperature dependence of the NDR behavior further supports this hypothesis

Reservoir Computing Approach to Robust Computation using Unreliable Nanoscale Networks

As we approach the physical limits of CMOS technology, advances in materials science and nanotechnology are making available a variety of unconventional computing substrates that can potentially replace top-down-designed silicon-based computing devices. Inherent stochasticity in the fabrication process and nanometer scale of these substrates inevitably lead to design variations, defects, faults, and noise in the resulting devices. A key challenge is how to harness such devices to perform robust computation. We propose reservoir computing as a solution. In reservoir computing, computation takes place by translating the dynamics of an excited medium, called a reservoir, into a desired output. This approach eliminates the need for external control and redundancy, and the programming is done using a closed-form regression problem on the output, which also allows concurrent programming using a single device. Using a theoretical model, we show that both regular and irregular reservoirs are intrinsically robust to structural noise as they perform computation

Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis.

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy

Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity.

Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca(2+) handling, we performed a chemical suppressor screen on zebrafish tremblor embryos, which suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the transfer of Ca(2+) from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+) sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and irregular contractions. We further show that overexpression of VDAC2 recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2 deficiency attenuates efsevin\u27s rescue effect and that VDAC2 functions synergistically with MCU to suppress cardiac fibrillation in tremblor. Together, these findings demonstrate a critical modulatory role for VDAC2-dependent mitochondrial Ca(2+) uptake in the regulation of cardiac rhythmicity

Feasibility and safety of GliaSite brachytherapy in treatment of CNS tumors following neurosurgical resection

Purpose: To investigate feasibility and safety of GliaSite brachytherapy for treatment of central nervous system (CNS) tumors following neurosurgical resection. We report mature results of long-term follow-up, outcomes and toxicity. Materials and Methods: In the period from 2004 to 2007, 10 consecutive adult patients with recurrent, newly diagnosed, and metastatic brain malignancies underwent GliaSite brachytherapy following maximally safe neurosurgical resection. While 6/10 (60%) patients were treated for recurrence, having previously been treated with external beam radiotherapy (EBRT), 4/10 (40%) received radiotherapy (RT) for the first time. A median dose of 52.0 Gy (range, 45.0 - 60.0 Gy) was prescribed to 0.5 cm - 1.0 cm from the balloon surface. Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicities associated with this technique. Follow-up was assessed with MRI scans and was available on all enrolled patients. Results: Median follow-up was 38 months (range, 18 - 57 months). Mean size of GliaSite balloon was 3.4 cm (range, 2.0 - 4.0 cm). Median survival was 14.0 months for the entire cohort after the treatment. The 17.6 and 16.0 months average survival for newly diagnosed and recurrent high grade gliomas (HGG), respectively, translated into a three-month improvement in survival in patients with newly diagnosed HGG compared to historical controls (P = 0.033). There were no RTOG grades 3 or 4 acute or late toxicities. Follow-up magnetic resonance imaging (MRI) imaging did not identify radiation necrosis. Conclusions: Our data indicate that treatment with GliaSite brachytherapy is feasible, safe and renders acceptable local control, acute and long-term toxicities. We are embarking on testing larger numbers of patients with this treatment modality

Nanocharacterization in Dentistry

About 80% of US adults have some form of dental disease. There are a variety of new dental products available, ranging from implants to oral hygiene products that rely on nanoscale properties. Here, the application of AFM (Atomic Force Microscopy) and optical interferometry to a range of dentistry issues, including characterization of dental enamel, oral bacteria, biofilms and the role of surface proteins in biochemical and nanomechanical properties of bacterial adhesins, is reviewed. We also include studies of new products blocking dentine tubules to alleviate hypersensitivity; antimicrobial effects of mouthwash and characterizing nanoparticle coated dental implants. An outlook on future “nanodentistry” developments such as saliva exosomes based diagnostics, designing biocompatible, antimicrobial dental implants and personalized dental healthcare is presented

Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders

Psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder are often accompanied by metabolic dysfunction symptoms, including obesity and diabetes. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In this review paper, we highlight the role of circadian clocks in glucocorticoid, dopamine, and orexin/melanin-concentrating hormone systems and describe how a dysfunction of these clocks may contribute to the simultaneous development of psychiatric and metabolic symptoms