Biomedical Lance Ion Sensitive System

The fabrication of a pH sensor which can be used in practical applications in biological and niedical fields was designed and manufactured using a new lance style ion sensitive field effect transistor. The lance can be used to measure pH levels in micro biological cultures without disruption of the culture and can be a powerful tool in real time Invitro medical diagnostics tool. The reference electrode can be placed onto the chip by depositing a noble metal contact in the field region. This is referred as a Pseudo Reference Electrode, PRE. By bringing the PRE design closer to the membrane, the active test area for the ISFET will then be contained to the small perimeter of the gate. Also, with the PRE being very close to the gate membrane, a larger percentage of charged ions will interact with the membrane which can allow for a smaller gate membrane and still have strong sensitivity. The combination of these two benefits can create a very compact Perimeters PRE ISFET design. With this compact design, it can be implemented on a MEMS cantilever for new testing methods in the medical and biological fields. By combining the ISFET device at the tip of a cantilever, the device can be put into use to test with minimum impact. Deep silicon etching was attempted using a protective front side coat and a hot KOH bath to etch a patterned backside. Complications in preserving sensitive ISFET components needs to be resolved before completion of freestanding cantilever lance MEMS probe with ISFET sensor

Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach

The symptoms of malaria are brought about by blood-stage parasites, which are established when merozoites invade human erythrocytes. Our understanding of the molecular events that underpin erythrocyte invasion remains hampered by the short-period of time that merozoites are invasive. To address this challenge, a Plasmodium falciparum gamma-irradiated long-lived merozoite (LLM) line was developed and investigated. Purified LLMs invaded erythrocytes by an increase of 10–300 fold compared to wild-type (WT) merozoites. Using an integrated omics approach, we investigated the basis for the phenotypic difference. Only a few single nucleotide polymorphisms within the P. falciparum genome were identified and only marginal differences were observed in the merozoite transcriptomes. By contrast, using label-free quantitative mass-spectrometry, a significant change in protein abundance was noted, of which 200 were proteins of unknown function. We determined the relative molar abundance of over 1100 proteins in LLMs and further characterized the major merozoite surface protein complex. A unique processed MSP1 intermediate was identified in LLM but not observed in WT suggesting that delayed processing may be important for the observed phenotype. This integrated approach has demonstrated the significant role of the merozoite proteome during erythrocyte invasion, while identifying numerous unknown proteins likely to be involved in invasion

Identifying Effects and Applications of Fixed and Variable Speed Limits

In Indiana, distracted driving and unexpected queues have led to an increase in the amount of back-of-queue crashes, particularly on approach to work zones. This report presents new strategies for the assessment of both transportation safety and traffic operations using crowd-sourced probe vehicle data and a speed laser vehicle re-identification scheme. This report concludes by recommending strategies for the placement of variable speed limits (VSL) adjacent to work zones and suggestions for future research

Next Generation Traffic Signal Performance Measures: Leveraging Connected Vehicle Data

High-resolution connected vehicle (CV) trajectory and event data has recently become commercially available. With over 500 billion vehicle position records generated each month in the United States, these data sets provide unique opportunities to build on and expand previous advances on traffic signal performance measures and safety evaluation. This report is a synthesis of research focused on the development of CV-based performance measures. A discussion is provided on data requirements, such as acquisition, storage, and access. Subsequently, techniques to reference vehicle trajectories to relevant roadways and movements are presented. This allows for performance analyses that can range from the movement- to the system-level. A comprehensive suite of methodologies to evaluate signal performance using vehicle trajectories is then provided. Finally, uses of CV hard-braking and hard-acceleration event data to assess safety and driver behavior are discussed. To evaluate scalability and test the proposed techniques, performance measures for over 4,700 traffic signals were estimated using more than 910 million vehicle trajectories and 14 billion GPS points in all 50 states and Washington, D.C. The contents of this report will help the industry transition towards a hybrid blend of detector- and CV-based signal performance measures with rigorously defined performance measures that have been peer-reviewed by both academics and industry leaders

Verification of a Fully Implicit Particle-in-Cell Method for the v∥v_\parallel Formalism of Electromagnetic Gyrokinetics in the XGC Code

A fully implicit particle-in-cell method for handling the $v_\parallel$-formalism of electromagnetic gyrokinetics has been implemented in XGC. By choosing the $v_\parallel$-formalism, we avoid introducing the non-physical skin terms in Amp\`{e}re's law, which are responsible for the well-known ``cancellation problem" in the $p_\parallel$-formalism. The $v_\parallel$-formalism, however, is known to suffer from a numerical instability when explicit time integration schemes are used due to the appearance of a time derivative in the particle equations of motion from the inductive component of the electric field. Here, using the conventional $\delta f$ scheme, we demonstrate that our implicitly discretized algorithm can provide numerically stable simulation results with accurate dispersive properties. We verify the algorithm using a test case for shear Alfv\'{e}n wave propagation in addition to a case demonstrating the ITG-KBM transition. The ITG-KBM transition case is compared to results obtained from other $\delta f$ gyrokinetic codes/schemes, whose verification has already been archived in the literature

Leveraging High Resolution Signalized Intersection Data to Characterize Discharge Headway Distributions and Saturation Flow Rate Reliability

As highway systems become more congested, it becomes increasingly important to understand the reliability with which we can estimate important performance measures such as volume to capacity ratios, particularly as we move toward leveraging field infrastructure to obtain real-time performance measures. In 1947, Greenshields wrote a paper that characterized “green time consumed” by “car-in-line-number” that ultimately was called headway. Average headway is one of principles used by the highway capacity manual to estimate saturation flow rate at signalized intersections. However, the current analytical techniques calculate a deterministic value for saturation flow rate that does not consider the stochastic variation of saturation flow rate. This paper reviews techniques used to estimate saturation flow rate, and proposes enhanced calculation methods to group saturation flow rate estimates by queue length. Grouping saturation flow rate estimates by queue length provides a convenient framework to evaluate saturation flow rate reliability. The inter-quartile range (25% - 75%) of saturation flow rates was calculated to be 1000vph based on Greenshields’ calculation techniques. Using the proposed enhanced calculation characterizing saturation flow rate, the inter-quartile range of saturation flow rate was shown to decrease from approximately 400 vph with 5 cars in a queue to 300 vph with 10 cars in queue. Because saturation flow rate is a fundamental input to volume-to-capacity performance measures, characterizing the stochastic variation of saturation flow rates provides a basic input for assessing how reliably one can estimate important performance measures such as volume-to-capacity ratios, as well as other performance measures that build upon volume-to-capacity ratios

Exposure-Dependent Control of Malaria-Induced Inflammation in Children

In malaria-naïve individuals, Plasmodium falciparum infection results in high levels of parasite-infected red blood cells (iRBCs) that trigger systemic inflammation and fever. Conversely, individuals in endemic areas who are repeatedly infected are often asymptomatic and have low levels of iRBCs, even young children. We hypothesized that febrile malaria alters the immune system such that P. falciparum re-exposure results in reduced production of pro-inflammatory cytokines/chemokines and enhanced anti-parasite effector responses compared to responses induced before malaria. To test this hypothesis we used a systems biology approach to analyze PBMCs sampled from healthy children before the six-month malaria season and the same children seven days after treatment of their first febrile malaria episode of the ensuing season. PBMCs were stimulated with iRBC in vitro and various immune parameters were measured. Before the malaria season, children's immune cells responded to iRBCs by producing pro-inflammatory mediators such as IL-1β, IL-6 and IL-8. Following malaria there was a marked shift in the response to iRBCs with the same children's immune cells producing lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines (IL-10, TGF-β). In addition, molecules involved in phagocytosis and activation of adaptive immunity were upregulated after malaria as compared to before. This shift was accompanied by an increase in P. falciparum-specific CD4+Foxp3- T cells that co-produce IL-10, IFN-γ and TNF; however, after the subsequent six-month dry season, a period of markedly reduced malaria transmission, P. falciparum-inducible IL-10 production remained partially upregulated only in children with persistent asymptomatic infections. These findings suggest that in the face of P. falciparum re-exposure, children acquire exposure-dependent P. falciparum-specific immunoregulatory responses that dampen pathogenic inflammation while enhancing anti-parasite effector mechanisms. These data provide mechanistic insight into the observation that P. falciparum-infected children in endemic areas are often afebrile and tend to control parasite replication

A live-attenuated chlamydial vaccine protects against trachoma in nonhuman primates

In cynomolgus macaques, ocular infection with a live trachoma strain lacking the conserved 7.5-kb plasmid induced no ocular pathology but facilitated solid or partial protection from subsequent infection with a virulent strain of trachoma

Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function

Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic malaria exposure is associated with a large increase in atypical memory B cells (MBCs) that resemble B cells expanded in a variety of persistent viral infections. Understanding the function of atypical MBCs and their relationship to classical MBCs will be critical to developing effective vaccines for malaria and other chronic infections. We show that VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable indicating a common developmental history. Atypical MBCs express an array of inhibitory receptors and B cell receptor (BCR) signaling is stunted in atypical MBCs resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion. Thus, in response to chronic malaria exposure, atypical MBCs appear to differentiate from classical MBCs becoming refractory to BCR-mediated activation and potentially interfering with the acquisition of malaria immunity. DOI: http://dx.doi.org/10.7554/eLife.07218.00