Rapid and specific diagnostic techniques are needed to expedite specific treatment of bacterial skin infections with narrow-spectrum antibiotics, rather than broad-spectrum. Through this work a device was developed to determine the presence of and species responsible for a bacterial skin infection using differences in Mie scatter spectra created by different bacterial species. A 650 nm LED at five different incident angles is used to illuminate the tissue, with Mie scatter being detected by PIN photodiodes at eight different detection angles. Mie scatter patterns are collected at all photodiode angles for each of the incident light angles, resulting in a Mie scatter spectra. Detectable differences in Mie scatter spectra were found using the device developed between commensal bacteria (no infection) and bacteria inoculated (infection) on the surface of both porcine and human cadaveric epidermis. Detectable differences were found between species of infection, specifically Escherichia coli and Staphylococcus aureus, with differences summarized through principle component analysis. Mie scatter spectra can be detected within a few seconds without skin contact. This device is the first to rapidly and specifically diagnose bacterial skin infections in a contact-less manner, allowing for initial treatment with narrow spectrum antibiotics, and helping to reduce the likelihood of resistance.

Endocytic processes are critical for cellular entry of several viruses; however, the role of endocytosis in cellular trafficking of viruses beyond virus entry is only partially understood. Here, we utilized two laboratory strains (AD169 and Towne) of human cytomegalovirus (HCMV), which are known to use cell membrane fusion rather than endocytosis to enter fibroblasts, in order to study a post-entry role of endocytosis in HCMV life cycle. Upon pharmacological inhibition of dynamin-2 or clathrin terminal domain (TD) ligand association, these strains entered the cells successfully based on the expression of immediate early viral protein. However, both the inhibitors significantly reduced the growth rates and final virus yields of viruses without inhibiting the expression of early to late viral proteins. Clathrin accumulated in the cytoplasmic virus assembly compartment (vAC) of infected cells co-localizing with virus tegument protein pp150 and the formation of vAC was compromised upon endocytic inhibition. Transmission electron micrographs (TEM) of infected cells treated with endocytosis inhibitors showed intact nuclear stages of nucleocapsid assembly but the cytoplasmic virus maturation was greatly compromised. Thus, the data presented here implicate endocytic pathways in HCMV maturation and egress.

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.

The transversal profile of beams can always be defined as a superposition of orthogonal fields, such as optical eigenmodes. Here, we describe a generic method to separate the individual components in a laser beam and map each mode onto its designated detector with low crosstalk. We demonstrate this with the decomposition into Laguerre-Gaussian beams and introduce a distribution over the integer numbers corresponding to the discrete orbital and radial momentum components of the light field. The method is based on determining an eigenmask filter transforming the incident optical eigenmodes to position eigenmodes enabling the detection of the state of the light field using single detectors while minimizing cross talk with respect to the set of filter masks considered.

The role of magmatic processes as a significant mechanism for the generation of voluminous silicic crust and the development of Cordilleran plateaus remains a lingering question in part because of the inherent difficulty in quantifying plutonic volumes. Despite this difficulty, a growing body of independently measured plutonic-to-volcanic ratios suggests the volume of plutonic material in the crust related to Cordilleran magmatic systems is much larger than is previously expected. To better examine the role of crustal magmatic processes and its relationship to erupted material in Cordilleran systems, we present a continuous high-resolution crustal seismic velocity model for an similar to 800 km section of the active South American Cordillera (Puna Plateau). Although the plutonic-to-volcanic ratios we estimate vary along the length of the Puna Plateau, all ratios are larger than those previously reported (similar to 30: 1 compared to 5: 1) implying that a significant volume of intermediate to silicic plutonic material is generated in the crust of the central South American Cordillera. Furthermore, as Cordilleran-type margins have been common since the onset of modern plate tectonics, our findings suggest that similar processes may have played a significant role in generating and/or modifying large volumes of continental crust, as observed in the continents today.

How FACs-producing generalist and specialist herbivores regulate their FACs-hydrolyzing enzyme L-ACY-1 to balance FACs' beneficial vs. detrimental effects remains unknown. To address this question, we compared L-ACY-1 expression in Helicoverpa armigera and Helicoverpa assulta, a pair of closely related sibling species differing mainly in their host range, by the same sets of hostplants, protein to digestible carbohydrate (P:C) ratios, or allelochemical. L-ACY-1 expression remained low/unchanged in H. armigera, but was induced by hot pepper fruits and repressed by cotton bolls in H. assulta. The representative allelochemicals of the tested hostplants significantly (capsaicin) or insignificantly (gossypol and nicotine) induced L-ACY-1 expression in H. armigera, but insignificantly inhibited (capsaicin and gossypol) or induced (nicotine) it in H. assulta. L-ACY-1 expression remained low/unaltered on balanced (P50:C50 and P53:C47) or protein-biased diets and induced on carbohydrate-biased diets in H. armigera, but was at the highest level on balanced diets and reduced on either protein-or carbohydrate-biased diets in H. assulta. Furthermore, L-ACY-1 expression was significantly higher in H. assulta than in H. armigera for most of feeding treatments. Such expressional divergences suggest that FACs are utilized mainly for removal of excessive nitrogen in generalists but for nitrogen assimilation in specialists.

Insufficient sleep is a global public health problem resulting in catastrophic accidents, increased mortality, and hundreds of billions of dollars in lost productivity. Yet the effect of sleep deprivation (SD) on decision making and performance is often underestimated by fatigued individuals and is only beginning to be understood by scientists. The deleterious impact of SD is frequently attributed to lapses in vigilant attention, but this account fails to explain many SD-related problems, such as loss of situational awareness and perseveration. Using a laboratory study protocol, we show that SD individuals can maintain information in the focus of attention and anticipate likely correct responses, but their use of such a top-down attentional strategy is less effective at preventing errors caused by competing responses. Moreover, when the task environment requires flexibility, performance under SD suffers dramatically. The impairment in flexible shifting of attentional control we observed is distinct from lapses in vigilant attention, as corroborated by the specificity of the influence of a genetic biomarker, the dopaminergic polymorphism DRD2 C957T. Reduced effectiveness of top-down attentional control under SD, especially when conditions require flexibility, helps to explain maladaptive performance that is not readily explained by lapses in vigilant attention.

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm(3) to 62 mm(3), even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

Accumulation of head impacts may contribute to acute and long-term brain trauma. Wearable sensors can measure impact exposure, yet current sensors do not have validated impact detection methods for accurate exposure monitoring. Here we demonstrate a head impact detection method that can be implemented on a wearable sensor for detecting field football head impacts. Our method incorporates a support vector machine classifier that uses biomechanical features from the time domain and frequency domain, as well as model predictions of head-neck motions. The classifier was trained and validated using instrumented mouthguard data from collegiate football games and practices, with ground truth data labels established from video review. We found that low frequency power spectral density and wavelet transform features (10 similar to 30 Hz) were the best performing features. From forward feature selection, fewer than ten features optimized classifier performance, achieving 87.2% sensitivity and 93.2% precision in cross-validation on the collegiate dataset (n = 387), and over 90% sensitivity and precision on an independent youth dataset (n = 32). Accurate head impact detection is essential for studying and monitoring head impact exposure on the field, and the approach in the current paper may help to improve impact detection performance on wearable sensors.

Cry1A insecticidal toxins bind sequentially to different larval gut proteins facilitating oligomerization, membrane insertion and pore formation. Cry1Ac interaction with cadherin triggers oligomerization. However, a mutation in an ABC transporter gene (ABCC2) is linked to Cry1Ac resistance in Plutella xylostella. Cry1AcMod, engineered to lack helix alpha-1, was able to form oligomers without cadherinbinding and effectively countered Cry1Ac resistance linked to ABCC2. Here we analyzed Cry1Ac and Cry1AcMod binding and oligomerization by western blots using brush border membrane vesicles (BBMV) from a strain of P. xylostella susceptible to Cry1Ac (Geneva 88) and a strain with resistance to Cry1Ac (NO-QAGE) linked to an ABCC2 mutation. Resistance correlated with lack of specific binding and reduced oligomerization of Cry1Ac in BBMV from NO-QAGE. In contrast, Cry1AcMod bound specifically and still formed oligomers in BBMV from both strains. We compared association of pre-formed Cry1Ac oligomer, obtained by incubating Cry1Ac toxin with a Manduca sexta cadherin fragment, with BBMV from both strains. Our results show that pre-formed oligomers associate more efficiently with BBMV from Geneva 88 than with BBMV from NO-QAGE, indicating that the ABCC2 mutation also affects the association of Cry1Ac oligomer with the membrane. These data indicate, for the first time, that ABCC2 facilitates Cry1Ac oligomerization and oligomer membrane insertion in P. xylostella.