Tunable Spin Injection in High-Quality Graphene with One-Dimensional Contacts.

Spintronics involves the development of low-dimensional electronic systems with potential use in quantum-based computation. In graphene, there has been significant progress in improving spin transport characteristics by encapsulation and reducing impurities, but the influence of standard two-dimensional (2D) tunnel contacts, via pinholes and doping of the graphene channel, remains difficult to eliminate. Here, we report the observation of spin injection and tunable spin signal in fully encapsulated graphene, enabled by van der Waals heterostructures with one-dimensional (1D) contacts. This architecture prevents significant doping from the contacts, enabling high-quality graphene channels, currently with mobilities up to 130 000 cm2 V-1 s-1 and spin diffusion lengths approaching 20 µm. The nanoscale-wide 1D contacts allow spin injection both at room and at low temperature, with the latter exhibiting efficiency comparable with 2D tunnel contacts. At low temperature, the spin signals can be enhanced by as much as an order of magnitude by electrostatic gating, adding new functionality.

Microwave-Frequency Scanning Gate Microscopy of a Si/SiGe Double Quantum Dot.

Conventional transport methods provide quantitative information on spin, orbital, and valley states in quantum dots but lack spatial resolution. Scanning tunneling microscopy, on the other hand, provides exquisite spatial resolution at the expense of speed. Working to combine the spatial resolution and energy sensitivity of scanning probe microscopy with the speed of microwave measurements, we couple a metallic tip to a Si/SiGe double quantum dot (DQD) that is integrated with a charge detector. We first demonstrate that the dc-biased tip can be used to change the occupancy of the DQD. We then apply microwaves through the tip to drive photon-assisted tunneling (PAT). We infer the DQD level diagram from the frequency and detuning dependence of the tunneling resonances. These measurements allow the resolution of ∼65 µeV excited states, an energy consistent with valley splittings in Si/SiGe. This work demonstrates the feasibility of scanning gate experiments with Si/SiGe devices.

Stable isotope ecology of black rhinos (Diceros bicornis) in Kenya.

Stable isotope and elemental ratios in hair are influenced by the environment, including both climate and geology. Stable carbon isotopes can be used to give estimates of the C4/CAM fraction of diets of herbivorous mammals; stable nitrogen isotopes are related to the local water deficit; strontium isotopes are determined by the local geology. We studied hair from rhinos in Kenya to determine spatial patterns in δ13C, δ15N, and 87Sr/86Sr ratios. The samples of rhino hair were collected during Kenya Wildlife Service translocation or veterinary activities. δ13C values showed diets dominated by C3 foods, but in some regions the diet, at least seasonally, contained significant quantities (i.e., > ca. 20%) of C4/CAM foods. δ15N values were related to water deficit, with higher δ15N values in regions with high water deficit. 87Sr/86Sr isotope ratios were found to be related to the local geological substrate suggesting that 87Sr/86Sr isotope ratios are provisionally useful for determining the origins of illegal wildlife materials in Kenya and elsewhere in Africa.

High order discretization techniques for real-space ab initio simulations.

In this paper, we present discretization techniques to address numerical problems that arise when constructing ab initio approximations that use real-space computational grids. We present techniques to accommodate the singular nature of idealized nuclear and idealized electronic potentials, and we demonstrate the utility of using high order accurate grid based approximations to Poisson's equation in unbounded domains. To demonstrate the accuracy of these techniques, we present results for a Full Configuration Interaction computation of the dissociation of H2 using a computed, configuration dependent, orbital basis set.

A Targeted Approach to Ligament Balancing Using Kinetic Sensors.

BACKGROUND: Currently, soft-tissue imbalance contributes to several of the foremost reasons for revision following primary TKA, including instability, stiffness, and aseptic loosening. In order to decrease the incidence of soft-tissue imbalance, intraoperative sensors were developed to provide real-time, quantitative load data within the knee. This study examines the intraoperative data of a group of multicenter patients to determine how targeted ligament releases affect intra-articular loading, and to understand which types of releases are necessary to achieve quantified ligament balance. METHODS: A group of 129 patients received sensor-assisted TKA, as part of a multicenter study. Medial and lateral loading data were collected pre-release, during any sequential releases, and post-release. All data were collected at 10°, 45°, and 90° during range of motion testing. Ligament release type, release technique type, and resultant loading were collected. RESULTS: Loading across the joint decreased, overall, and became more symmetrical after releases were performed. On average, between 2 and 3 corrections were made (up to 8) in order to achieve ligament balance. The ligament release type and subsequent quantified change in loading were in agreement with historical, qualified sources. CONCLUSION: Objective data from sensor output may assist surgeons in decreasing loading variability and, thereby, decreasing ligament imbalance and its associated complications.

Characterization of space dust using acoustic impact detection.

This paper describes studies leading to the development of an acoustic instrument for measuring properties of micrometeoroids and other dust particles in space. The instrument uses a pair of easily penetrated membranes separated by a known distance. Sensors located on these films detect the transient acoustic signals produced by particle impacts. The arrival times of these signals at the sensor locations are used in a simple multilateration calculation to measure the impact coordinates on each film. Particle direction and speed are found using these impact coordinates and the known membrane separations. This ability to determine particle speed, direction, and time of impact provides the information needed to assign the particle's orbit and identify its likely origin. In many cases additional particle properties can be estimated from the signal amplitudes, including approximate diameter and (for small particles) some indication of composition/morphology. Two versions of this instrument were evaluated in this study. Fiber optic displacement sensors are found advantageous when very thin membranes can be maintained in tension (solar sails, lunar surface). Piezoelectric strain sensors are preferred for thicker films without tension (long duration free flyers). The latter was selected for an upcoming installation on the International Space Station.

A new method for defining balance: promising short-term clinical outcomes of sensor-guided TKA.

Recently, technological advances have made it possible to quantify pounds of pressure across the bearing surface during TKA. This multicenter evaluation, using intraoperative sensors, was performed for two reasons: 1) to define "balance" 2) to determine if patients with balanced knees exhibit improved short-term clinical outcomes. Outcomes scores were compared between "balanced" and "unbalanced" patients. At 6-months, the balanced cohort scored 172.4 and 14.5 in KSS and WOMAC, respectively; the unbalanced cohort scored 145.3 and 23.8 in KSS and WOMAC (P < 0.001). Out of all confounding variables, balanced joints were the most significant contributing factor to improved postoperative outcomes (P < 0.001). Odds ratios demonstrate that balanced joints are 2.5, 1.3, and 1.8 times more likely to achieve meaningful improvement in KSS, WOMAC, and activity level, respectively.

The Interplay of Binary and Quantitative Structure on the Stability of Mutualistic Networks.

Understanding how the structure of biological systems impacts their resilience (broadly defined) is a recurring question across multiple levels of biological organization. In ecology, considerable effort has been devoted to understanding how the structure of interactions between species in ecological networks is linked to different broad resilience outcomes, especially local stability. Still, nearly all of that work has focused on interaction structure in presence-absence terms, and has not investigated quantitative structure, i.e., the arrangement of interaction strengths in ecological networks. We investigated how the interplay between binary and quantitative structure impacts stability in mutualistic interaction networks (those in which species interactions are mutually beneficial), using community matrix approaches. We additionally examined the effects of network complexity and within-guild competition for context. In terms of structure, we focused on understanding the stability impacts of nestedness, a structure in which more-specialized species interact with smaller subsets of the same species that more-generalized species interact with. Most mutualistic networks in nature display binary nestedness, which is puzzling because both binary and quantitative nestedness are known to be destabilizing on their own. We found that quantitative network structure has important consequences for local stability. In more-complex networks, binary-nested structures were the most stable configurations, depending on the quantitative structures; but which quantitative structure was stabilizing depended on network complexity and competitive context. As complexity increases, and in the absence of within-guild competition, the most stable configurations have a nested binary structure with a complementary (i.e., anti-nested) quantitative structure. In the presence of within-guild competition, however, the most stable networks are those with a nested binary structure and a nested quantitative structure. In other words, the impact of interaction-overlap on community persistence is dependent on the competitive context. These results help to explain the prevalence of binary nested structures in nature and underscore the need for future empirical work on quantitative structure.

Exploring room temperature spin transport under band gap opening in bilayer graphene.

We study the room-temperature electrical control of charge and spin transport in high-quality bilayer graphene, fully encapsulated with hBN and contacted via 1D spin injectors. We show that spin transport in this device architecture is measurable at room temperature and its spin transport parameters can be modulated by opening of a band gap via a perpendicular displacement field. The modulation of the spin current is dominated by the control of the spin relaxation time with displacement field, demonstrating the basic operation of a spin-based field-effect transistor.

Capillary sprout endothelial cells exhibit a CD36 low phenotype: regulation by shear stress and vascular endothelial growth factor-induced mechanism for attenuating anti-proliferative thrombospondin-1 signaling.

Endothelial cells acquire distinctive molecular signatures in their transformation to an angiogenic phenotype that are indicative of changes in cell behavior and function. Using a rat mesentery model of inflammation-induced angiogenesis and a panel of known endothelial markers (CD31, VE-cadherin, BS-I lectin), we identified a capillary sprout-specific endothelial phenotype that is characterized by the marked down-regulation of CD36, a receptor for the anti-angiogenic molecule thrombospondin-1 (TSP-1). TSP-1/CD36 interactions were shown to regulate angiogenesis in this model as application of TSP-1 inhibited angiogenesis and blockade of both TSP-1 and CD36 accelerated angiogenesis. Vascular endothelial growth factor, which was up-regulated in the in vivo model, elicited a dose- and time-dependent down-regulation of CD36 (ie, to a CD36 low phenotype) in cultured human umbilical vein endothelial cells. Human umbilical vein endothelial cells that had been conditioned to a CD36 low phenotype with VEGF were found to be refractory to anti-proliferative TSP-1 signaling via a CD36-dependent mechanism. The loss of exposure to wall shear stress, which occurs in vivo when previously quiescent cells begin to sprout, also generated a CD36 low phenotype. Ultimately, our results identified the regulation of endothelial cell CD36 expression as a novel mechanism through which VEGF stimulates and sustains capillary sprouting in the presence of TSP-1. Additionally, CD36 was shown to function as a potential molecular linkage through which wall shear stress may regulate both microvessel sprouting and quiescence.

The use of a binary chelate formulation: Could gadolinium based linear contrast agents be rescued by the addition of zinc selective chelates?

Tissue and bone retention of gadolinium based contrast agents (GBCAs) has become a clinical concern because of the potential short and long term toxic effects of free gadolinium. This is a critical problem for most open-chain agents that more readily transmetallate in vivo, in comparison to macrocyclic compounds. Gadolinium diethylene tri-aminepentaacetic acid bis-glucosamide (Gd-DTPA-BIGA) is an experimental, open-chain contrast agent which has a significantly increased relaxivity coefficient in comparison to other GBCAs. This results in greater signal intensity and improved contrast enhancement. These superior imaging qualities initiated a search for a solution to the transmetallation of this agent. Plasma zinc is a well-known GBCA transmettalation agent. Since the base chelate of Gadodiamide (Gd-DPTA-Bis-Methylamide or Omniscan), DTPA-Bis-Methylamide (DTPA-BMA), readily transmettalates with and binds serum zinc, we hypothesized that a plasma "zinc sink," may significantly reduce transmetallation of linear agents. 5% DTPA-BMA was added to a formulation of Gd-DTPA-BIGA, which was tested against the original formulation of Gd-DTPA-BIGA with 0.2% of the base chelate DTPA-BIGA. These formulations, including gadodiamide, were labeled with 153GdCl3 followed by infusion into cohorts of Sprague Dawley rats which were sacrificed at 1, 30 and 60 days. Internal organs were harvested, along with blood, skin and femur, and analyzed for residual gadolinium. A subset of tissues were also interrogated with ICP-MS. Labeled Gadodiamide and saline where used as controls. Conclusion: The addition of 5% DTPA-BMA, as a zinc binding agent, reduced the transmetallation of the linear agent Gd-DTPA-BIGA, in comparison to its original formulation supplemented with 0.2% BIGA. This result indicates that supplementing linear GBCAs with ancillary chelates may hold promise for reducing, or eliminating the biological archiving of gadolinium in tissues. In addition, this paper provides valuable animal data on the long term retention of gadolinium from linear based contrast agents.

Optimizing the alignment of thermoresponsive poly(N-isopropyl acrylamide) electrospun nanofibers for tissue engineering applications: A factorial design of experiments approach.

Thermoresponsive polymers, such as poly(N-isopropyl acrylamide) (PNIPAM), have been identified and used as cell culture substrates, taking advantage of the polymer's lower critical solution temperature (LCST) to mechanically harvest cells. This technology bypasses the use of biochemical enzymes that cleave important cell-cell and cell-matrix interactions. In this study, the process of electrospinning is used to fabricate and characterize aligned PNIPAM nanofiber scaffolds that are biocompatible and thermoresponsive. Nanofiber scaffolds produced by electrospinning possess a 3D architecture that mimics native extracellular matrix, providing physical and chemical cues to drive cell function and phenotype. We present a factorial design of experiments (DOE) approach to systematically determine the effects of different electrospinning process parameters on PNIPAM nanofiber diameter and alignment. Results show that high molecular weight PNIPAM can be successfully electrospun into both random and uniaxially aligned nanofiber mats with similar fiber diameters by simply altering the speed of the rotating mandrel collector from 10,000 to 33,000 RPM. PNIPAM nanofibers were crosslinked with OpePOSS, which was verified using FTIR. The mechanical properties of the scaffolds were characterized using dynamic mechanical analysis, revealing an order of magnitude difference in storage modulus (MPa) between cured and uncured samples. In summary, cross-linked PNIPAM nanofiber scaffolds were determined to be stable in aqueous culture, biocompatible, and thermoresponsive, enabling their use in diverse cell culture applications.

Endothelial Cell Phenotypes are Maintained During Angiogenesis in Cultured Microvascular Networks.

A challenge in tissue engineering biomimetic models for studying angiogenesis is building the physiological complexity of real microvascular networks. Our laboratory recently introduced the rat mesentery culture model as an ex vivo experimental platform for investigating multicellular dynamics involved in angiogenesis within intact microvascular networks. The objective of this study was to compare endothelial cell phenotypes along capillary sprouts in cultured ex vivo rat mesentery microvascular networks to in vivo endothelial cell phenotypes. For Day 3 (Ex Vivo) tissues, adult rat mesentery tissues were cultured for three days in media supplemented with 10% serum. For Day 3 (In Vivo) tissues, adult rats were anesthetized and the mesentery was exteriorized for twenty minutes to induce angiogenesis. Microvascular networks from Day 3 (Ex Vivo) and Day 3 (In Vivo) groups were angiogenic, characterized by an increase in vessel density, capillary sprouting, and identification of similar BrdU-positive endothelial cell distributions along sprouts. Endothelial cells in both groups extended pseudopodia at the distal edge of capillary sprouts and displayed similar endothelial cell UNC5b, VEGFR-2, and CD36 labeling patterns. The results from this study support the physiological relevance of the rat mesentery culture model and highlight its novelty as a biomimetic tool for angiogenesis research.

Modulation of cell responses to Ag-(MeO2 MA-co-OEGMA): Effects of nanoparticle surface hydrophobicity and serum proteins on cellular uptake and toxicity.

Nanoparticle (NP) interactions with cellular systems are influenced by both NP physico-chemical properties and the presence of surface-bound proteins that are adsorbed in biological environments. Here, we characterize cellular responses to silver nanoparticles (AgNPs) functionalized with poly(di(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) methyl methacrylate) (poly(MeO2 MAx -co-OEGMAy )) brushes with tunable hydrophobicity and explore how these responses are modulated by the presence or absence of serum proteins. Poly(MeO2 MAx -co-OEGMAy ) with variable composition (5-10% OEGMA) was fabricated to elicit differential hydrophobicity at 37°C for AgNPs capped with these copolymers. The increase in Ag-(MeO2 MAx -co-OEGMAy ) surface hydrophobicity from (x:y) = 90:10 to (x:y) = 95:5 led to enhanced cytotoxicity of L-929 fibroblasts and a concomitant increase in cell uptake and reactive oxygen species generation in the presence of serum proteins. These responses were attenuated significantly in serum-free environments. Broad inhibition of PI3 kinase-mediated endocytosis reduced both cell uptake and cytotoxicity in the presence or absence of serum proteins. In contrast, selective inhibition of clathrin- and caveolae-mediated endocytosis markedly decreased cell uptake and cytotoxicity in response to Ag-(MeO2 MA95 -co-OEGMA5 ) exclusively in the presence of serum proteins, whereas cell responses to the more hydrophilic Ag-(MeO2 MA90 -co-OEGMA10 ) were less affected by the inhibition of these pathways with or without serum proteins. This study demonstrates an important role for both NP surface hydrophobicity and the presence of serum proteins in directing cell uptake and subsequent cellular responses, which we suggest has broad application in the design of polymer-functionalized NPs for specific biological outcomes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1061-1071, 2018.

Effects of Methacrylate-Based Thermoresponsive Polymer Brush Composition on Fibroblast Adhesion and Morphology.

Thermoresponsive polymers are being used increasingly in cell culture applications due to their temperature dependent surface properties. Poly(MEO2MA-co-OEGMA) (PMO) brushes offer tunable physical properties via variation in the copolymer ratio, but the effects of composition on cell-substrate interactions is unclear. To this end, a series of PMO brushes (0-8% OEGMA) was fabricated and L-929 fibroblast adhesion and morphology was quantified in the presence of serum (FBS) or after functionalization via the adsorption of fibronectin (FN) and vitronectin (VN). Quantification of the adsorption of model proteins, bovine serum albumin and FN, revealed that the extent of adsorption was correlated to the amount MEO2MA content, which represents the more hydrophobic component in PMO brushes. Cells exhibited delayed attachment and spreading on all PMO substrates in the presence of FBS. After 24 h, cell attachment was comparable; however, increased spreading was correlated with increased MEO2MA content. Adsorption of FN significantly increased initial cell attachment to all PMO surfaces after 2 h. This was not observed with VN; however, both FN and VN increased cell spreading/decreased cell circularity for all PMO substrates relative to FBS. Pure MEO2MA brushes with FN exhibited increased cell spreading/decreased cell circularity relative to other PMO substrates after 2 h, and elicited the highest cell density after 24 h. These results demonstrate that increased MEO2MA content in PMO substrates facilitates cell attachment and spreading, which can be further enhanced by adsorbing FN in the absence of other proteins.

Tuning reversible cell adhesion to methacrylate-based thermoresponsive polymers: Effects of composition on substrate hydrophobicity and cellular responses.

Thermoresponsive polymer (TRP) cell culture substrates are widely utilized for nonenzymatic, temperature-triggered release of adherent cells. Increasingly, multicomponent TRPs are being developed to facilitate refined control of cell adhesion and detachment, which requires an understanding of the relationships between composition-dependent substrate physicochemical properties and cellular responses. Here, we utilize a homologous series of poly(MEO2 MAx -co-OEGMAy ) brushes with variable copolymer ratio (x/y) to explore the effects of substrate hydrophobicity on L-929 fibroblast adhesion, morphology, and temperature-triggered cell detachment. Substrate hydrophobicity is reported in terms of the equilibrium spreading coefficient (S), and variations in copolymer ratio reveal differential hydrophobicity that is correlated to serum protein adsorption and initial cell attachment at 37°C. Furthermore, quantitative metrics of cell morphology show that cell spreading is enhanced on more hydrophobic surfaces with increased (x/y) ratio, which is further supported by gene expression analysis of biomarkers of cell spreading (e.g., RhoA, Dusp2). Temperature-dependent cell detachment is limited for pure poly(MEO2 MA); however, rapid cell rounding and detachment (<20 min) are evident for all poly(MEO2 MAx -co-OEGMAy ) substrates. These results suggest that increased MEO2 MA content in poly(MEO2 MAx -co-OEGMAy ) substrates elicits enhanced protein adsorption, cell adhesion, and cell spreading; however, integration of small amounts of the more hydrophilic OEGMA unit facilitates both cell attachment/spreading and detachment. This study demonstrates an important role for the composition-dependent control of surface hydrophobicity in the design of multicomponent TRPs for desired biological outcomes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2416-2428, 2017.

Small molecule inducers of angiogenesis for tissue engineering.

Engineering of implantable tissues requires rapid induction of angiogenesis to meet the significant oxygen and nutrient demands of cells during tissue repair. To this end, our laboratories have utilized medicinal chemistry to synthesize non-peptide-based inducers of angiogenesis to aid tissue engineering. In this study, we describe the evaluation of SC-3-149, a small molecule compound with proliferative effects on vascular endothelial cells. Specifically, exogenous exposure of SC-3-149 induced an 18-fold increase in proliferation of human microvascular endothelial cells in vitro at low micromolar potency by day 14 in culture. Moreover, SC-3-149 significantly increased the formation of endothelial cord and tubelike structures in vitro, and improved endothelial scratch wound healing within 24 h. SC-3-149 also significantly inhibited vascular endothelial cell death owing to serum deprivation and high acidity (pH 6). Concurrent incubation of SC-3-149 with vascular endothelial growth factor increased cell survivability under serum-deprived conditions by an additional 7%. In addition, in vivo injection of SC-3-149 into the rat mesentery produced qualitative increases in microvessel length density. Taken together, our studies suggest that SC-3-149 and its analogs may serve as promising new angiogenic agents for targeted drug delivery and therapeutic angiogenesis in tissue engineering.

A novel technique using sensor-based technology to evaluate tibial tray rotation.

Rotational tibiofemoral congruency and centralized patellar tracking are critical technical factors that affect the postoperative success of total knee arthroplasty (TKA). Several techniques are used to position the femoral component, but there is no validated method for achieving the ideal rotational position of the tibial component. It has been suggested that referencing the midmedial third of the tibial tubercle intraoperatively mitigates positional outliers. This study used data collected from intraoperative sensors to quantify the variability associated with using the midmedial third of the tibial tubercle in 170 patients undergoing primary TKA. With the sensor-equipped trial insert in place, the knee was taken into extension and the location of the femoral condylar contact point on the articular surface of the tibial insert was displayed. Rotational adjustments of the tibial tray were evaluated in real time as the surgeon corrected tray malpositioning. The initial and final angles of tibial tray rotation were captured and recorded with intraoperative video feed. When referencing the tubercle, 53% of patients had asymmetric tibiofemoral congruency in extension. Of those patients, 68% had excessive internal rotation of the tibial tray relative to the femur and 32% had excessive external rotation. The average tibiofemoral incongruency deviated from a neutral position by 6° (range, 0.5°-19.2°). Data from this evaluation suggest that use of the tibial tubercle to maximize tibiofemoral congruency is highly variable and inconsistent for confirming the final rotation of the tibial tray.

A Systematic Literature Review of Three Modalities in Technologically Assisted TKA.

In effort to reduce the revision burden of total knee arthroplasty (TKA), industry emphasis has focused on replacing manual techniques-which are subject to variability-with technological implements. Unfortunately, technological innovation often continues before adequate time for critical evaluation has passed. Therefore, the purpose of this descriptive literature review was to collect a large sample of international data and report on the clinical and economic efficacy of three major types of technologically assisted TKA: navigation, patient-specific instrumentation, and sensorized trials.