Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing.

Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. To-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. Here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. Porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. They exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. In in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. Flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial

Defeating David : looking beyond a matched strategy

This thesis builds upon existing contemporary theories that attempt to explain the outcomes of asymmetric conflict. Specifically, this thesis uses Ivan Arreguin-Toft's Strategic Interaction Theory as a baseline to identify theoretical gaps that can not only help further explain asymmetric conflict outcomes, but also provide insight into developing the proper strategy for strong actors. Arreguin-Toft contends that when the strong actor employs the correct strategy then it will win over 75 percent of conflicts against a materially weaker adversary. This leads to a fundamental question: if the strong actor uses the correct strategy against a weaker opponent, then why do strong actors still lose nearly 25 percent of the time? In an effort to identify other key variables that help explain non-conventional war outcomes, this thesis evaluates case studies where the strong actor both won and lost an asymmetric conflict after choosing the correct strategy. This study finds two other factors that are important to achieving victory in an asymmetric conflict. First, the strong actor must have a viable indigenous political authority to work by, with and through. This concept has little to do with political legitimacy. Instead, it focuses on the capacity of the host nation, with strong actor assistance, to synchronize its military and political effort to defeat the insurgency. Second, the strong actor must not only use restraint in applying direct military power, but it must also use the correct force: a cadre that is trained in conducting irregular warfare. As such, this thesis' conclusions are aligned with the belief that it is the host nation's war to win or lose-adhering to this principle provides the strong actor with the best chance of "defeating David" before losing its political will.http://archive.org/details/defeatingdavidlo1094510634US Air Force (USAF) author

Evaluating Active U: an Internet-mediated physical activity program.

Background: Engaging in regular physical activity can be challenging, particularly during the winter months. To promote physical activity at the University of Michigan during the winter months, an eight-week Internet-mediated program (Active U) was developed providing participants with an online physical activity log, goal setting, motivational emails, and optional team participation and competition. Methods: This study is a program evaluation of Active U. Approximately 47,000 faculty, staff, and graduate students were invited to participate in the online Active U intervention in the winter of 2007. Participants were assigned a physical activity goal and were asked to record each physical activity episode into the activity log for eight weeks. Statistics for program reach, effectiveness, adoption, and implementation were calculated using the Re-Aim framework. Multilevel regression analyses were used to assess the decline in rates of data entry and goal attainment during the program, to assess the likelihood of joining a team by demographic characteristics, to test the association between various predictors and the number of weeks an individual met his or her goal, and to analyze server load. Results: Overall, 7,483 individuals registered with the Active U website (≈16% of eligible), and 79% participated in the program by logging valid data at least once. Staff members, older participants, and those with a BMI < 25 were more likely to meet their weekly physical activity goals, and average rate of meeting goals was higher among participants who joined a competitive team compared to those who participated individually (IRR = 1.28, P < .001). Conclusion: Internet-mediated physical activity interventions that focus on physical activity logging and goal setting while incorporating team competition may help a significant percentage of the target population maintain their physical activity during the winter months

Ecosystem respiration: Drivers of daily variability and background respiration in lakes around the globe

We assembled data from a global network of automated lake observatories to test hypotheses regarding the drivers of ecosystem metabolism. We estimated daily rates of respiration and gross primary production (GPP) for up to a full year in each lake, via maximum likelihood fits of a free‐water metabolism model to continuous high‐frequency measurements of dissolved oxygen concentrations. Uncertainties were determined by a bootstrap analysis, allowing lake‐days with poorly constrained rate estimates to be down‐weighted in subsequent analyses. GPP and respiration varied considerably among lakes and at seasonal and daily timescales. Mean annual GPP and respiration ranged from 0.1 to 5.0 mg O2 L−1 d−1 and were positively related to total phosphorus but not dissolved organic carbon concentration. Within lakes, significant day‐to‐day differences in respiration were common despite large uncertainties in estimated rates on some lake‐days. Daily variation in GPP explained 5% to 85% of the daily variation in respiration after temperature correction. Respiration was tightly coupled to GPP at a daily scale in oligotrophic and dystrophic lakes, and more weakly coupled in mesotrophic and eutrophic lakes. Background respiration ranged from 0.017 to 2.1 mg O2 L−1 d−1 and was positively related to indicators of recalcitrant allochthonous and autochthonous organic matter loads, but was not clearly related to an indicator of the quality of allochthonous organic matter inputs

Lengthened Predelivery Stay and Antepartum Complications in Women with Depressive Symptoms During Pregnancy

Background: It is crucial to understand the timing and mechanisms behind depression's effect on peripartum stay because attempts to intervene will vary based on the time period involved. We designed this study to compare predelivery and postdelivery length of stay in women with and without elevated depressive symptoms during pregnancy. Methods: This study involved secondary data analysis of a larger study exploring antepartum depression. Each subject completed the Center for Epidemiological Studies Depression Scale (CES-D) during pregnancy at a mean of 25.8 weeks' gestation. We used time-stamped data to compare total peripartum, predelivery, and postdelivery lengths of stay in women with and without elevated depressive symptoms during pregnancy. In addition, we used a Cox proportional hazards regression model to evaluate potential mechanisms for depression's effect on length of stay. Results: The study sample included 802 pregnant women. Overall, 18% of study subjects scored >=16 on the CES-D. Bivariate analyses demonstrated a significant association between elevated depressive symptoms and longer predelivery stays (time from admission to delivery). Interaction analyses demonstrated a significant interaction effect between depressive symptoms and parity, such that depressive symptoms were significantly associated with predelivery length of stay in multiparas but not so in primiparous subjects. In a multivariate model of multiparous subjects, depression's effect on length of stay was partially influenced by sociodemographic confounders but remained significant until antepartum complications were added to the model. Conclusions: Depressive symptoms during pregnancy are significantly associated with a subsequent increase in predelivery length of stay, and this association is mediated in part by antepartum complications, even after controlling for sociodemographic factors. These longer hospital stays can present significant burdens to the patient, her family, and the healthcare system. Future studies should evaluate whether interventions for depression during pregnancy can impact this relationship among depressive symptoms during pregnancy, antepartum complications, and extensive predelivery hospitalizations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90486/1/jwh-2E2010-2E2380.pd

Intracellular soluble α-synuclein oligomers reduce pyramidal cell excitability

The presynaptic protein α-synuclein (αSyn) aggregates during Parkinson's disease (PD) to form large proteinaceous amyloid plaques, the spread of which throughout the brain clinically defines the severity of the disease. During early stages of aggregation, αSyn forms soluble annular oligomers that show greater toxicity than much larger fibrils. These oligomers produce toxicity via a number of possible mechanisms, including the production of pore-forming complexes that permeabilize membranes. In the present study, two well-defined species of soluble αSyn oligomers were produced by different protocols: by polymerization of monomer and by sonication of fibrils. The two oligomeric species produced were morphologically similar, with both having an annular structure and consisting of approximately the same number of monomer subunits, although they differed in their secondary structure. Oligomeric and monomeric αSyn were injected directly into the soma of pyramidal neurons in mouse neocortical brain slices during whole-cell patch clamp recording. Using a combined experimental and modelling approach, neuronal parameters were extracted to measure, for the first time in the neocortex, specific changes in neuronal electrophysiology. Both species of oligomer had similar effects: (i) a significant reduction in input resistance and the membrane time constant and (ii) an increase in the current required to trigger an action potential with a resultant reduction in the firing rate. Differences in oligomer secondary structure appeared to produce only subtle differences in the activity of the oligomers. Monomeric αSyn had no effect on neuronal parameters, even at high concentrations. The oligomer-induced fall in neuronal excitability has the potential to impact both network activity and cognitive processing

Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury

The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI

Salmonella typhimurium's transthyretin-like protein is a host-specific factor important in fecal survival in chickens.

The transthyretin-like protein (TLP) from Salmonella enterica subspecies I is a periplasmic protein with high level structural similarity to a protein found in mammals and fish. In humans, the protein homologue, transthyretin, binds and carries retinol and thyroxine, and a series of other, unrelated aromatic compounds. Here we show that the amino acid sequence of the TLP from different species, subspecies and serovars of the Salmonella genus is highly conserved and demonstrate that the TLP gene is constitutively expressed in S. Typhimurium and that copper and other divalent metal ions severely inhibit enzyme activity of the TLP, a cyclic amidohydrolase that hydrolyses 5-hydroxyisourate (5-HIU). In order to determine the in vivo role of the S. Typhimurium TLP, we constructed a strain of mouse-virulent S. Typhimurium SL1344 bearing a mutation in the TLP gene (SL1344 ΔyedX). We assessed the virulence of this strain via oral inoculation of mice and chickens. Whilst SL1344 ΔyedX induced a systemic infection in both organisms, the bacterial load detected in the faeces of infected chickens was significantly reduced when compared to the load of S. Typhimurium SL1344. These data demonstrate that the TLP gene is required for survival of S. Typhimurium in a high uric acid environment such as chicken faeces, and that metabolic traits of Salmonellae in natural and contrived hosts may be fundamentally different. Our data also highlight the importance of using appropriate animal models for the study of bacterial pathogenesis especially where host-specific virulence factors or traits are the subject of the study