l-Theanine as a Functional Food Additive: Its Role in Disease Prevention and Health Promotion

Tea has been consumed for thousands of years and is an integral part of people’s daily routine, as an everyday drink and a therapeutic aid for health promotion. Consumption of tea has been linked to a sense of relaxation commonly associated with the content of the non-proteinogenic amino acid theanine, which is found within the tea leaves. The aim of this review article is to outline the current methods for synthesis, extraction and purification of theanine, as well as to examine its potential benefits related to human health. These include improvements in cognitive and immune function, cancer prevention, reduced cardiovascular risk and its potential usefulness as a functional food product

Developing a Dissociative Nanocontainer for Peptide Drug Delivery

The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB) models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP) reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid) is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers

Brainwave profiles of efficient versus inefficient working memory retrievals inhealthy older adults

General slowing of mental processing speed is hallmark of brain and cognitive aging. Thus far it has been limited under-standing in neural mechanisms underlying mental states during fluctuations between efficient versus inefficient cognitiveperformance within individual older adults. Here we examined electrophysiological responses during visual working mem-ory retrieval trials that are fast versus slow reactions. Wireless EEG along with accuracy and reaction times were recordedduring a modified delayed match-to-sample task in 17 cognitively normal older adults (age 65-95) from North America.Compared to trials that are faster than averaged (mean 584 ms), the late positive potentials during trials that are slowerthan average (mean 747 ms) showed increased responses to memory nonmatch distractors than those to object matchingmemory targets in frontal sites, as previously reported in older brains. Interestingly, the brainwaves during efficient andaccurate memory retrievals resemble those typically seen in younger adults

Comparing Remote Sensing and Field-Based Approaches to Estimate Ladder Fuels and Predict Wildfire Burn Severity

While fire is an important ecological process, wildfire size and severity have increased as a result of climate change, historical fire suppression, and lack of adequate fuels management. Ladder fuels, which bridge the gap between the surface and canopy leading to more severe canopy fires, can inform management to reduce wildfire risk. Here, we compared remote sensing and field-based approaches to estimate ladder fuel density. We also determined if densities from different approaches could predict wildfire burn severity (Landsat-based Relativized delta Normalized Burn Ratio; RdNBR). Ladder fuel densities at 1-m strata and 4-m bins (1–4 m and 1–8 m) were collected remotely using a terrestrial laser scanner (TLS), a handheld-mobile laser scanner (HMLS), an unoccupied aerial system (UAS) with a multispectral camera and Structure from Motion (SfM) processing (UAS-SfM), and an airborne laser scanner (ALS) in 35 plots in oak woodlands in Sonoma County, California, United States prior to natural wildfires. Ladder fuels were also measured in the same plots using a photo banner. Linear relationships among ladder fuel densities estimated at broad strata (1–4 m, 1–8 m) were evaluated using Pearson’s correlation (r). From 1 to 4 m, most densities were significantly correlated across approaches. From 1 to 8 m, TLS densities were significantly correlated with HMLS, UAS-SfM and ALS densities and UAS-SfM and HMLS densities were moderately correlated with ALS densities. Including field-measured plot-level canopy base height (CBH) improved most correlations at medium and high CBH, especially those including UAS-SfM data. The most significant generalized linear model to predict RdNBR included interactions between CBH and ladder fuel densities at specific 1-m stratum collected using TLS, ALS, and HMLS approaches (R2 = 0.67, 0.66, and 0.44, respectively). Results imply that remote sensing approaches for ladder fuel density can be used interchangeably in oak woodlands, except UAS-SfM combined with the photo banner. Additionally, TLS, HMLS and ALS approaches can be used with CBH from 1 to 8 m to predict RdNBR. Future work should investigate how ladder fuel densities using our techniques can be validated with destructive sampling and incorporated into predictive models of wildfire severity and fire behavior at varying spatial scales

L-Edge Spectroscopy of Dilute, Radiation-Sensitive Systems Using a Transition-Edge-Sensor Array

We present X-ray absorption spectroscopy and resonant inelastic X-ray scattering (RIXS) measurements on the iron L-edge of 0.5 mM aqueous ferricyanide. These measurements demonstrate the ability of high-throughput transition-edge-sensor (TES) spectrometers to access the rich soft X-ray (100-2000eV) spectroscopy regime for dilute and radiation-sensitive samples. Our low-concentration data are in agreement with high-concentration measurements recorded by conventional grating-based spectrometers. These results show that soft X-ray RIXS spectroscopy acquired by high-throughput TES spectrometers can be used to study the local electronic structure of dilute metal-centered complexes relevant to biology, chemistry and catalysis. In particular, TES spectrometers have a unique ability to characterize frozen solutions of radiation- and temperature-sensitive samples.Comment: 19 pages, 4 figure

Reconstructing Words from Right-Bounded-Block Words

A reconstruction problem of words from scattered factors asks for the minimal information, like multisets of scattered factors of a given length or the number of occurrences of scattered factors from a given set, necessary to uniquely determine a word. We show that a word $w \in \{a, b\}^{*}$ can be reconstructed from the number of occurrences of at most $\min(|w|_a, |w|_b)+ 1$ scattered factors of the form $a^{i} b$. Moreover, we generalize the result to alphabets of the form $\{1,\ldots,q\}$ by showing that at most $\sum^{q-1}_{i=1} |w|_i (q-i+1)$ scattered factors suffices to reconstruct $w$. Both results improve on the upper bounds known so far. Complexity time bounds on reconstruction algorithms are also considered here

Visuohaptic convergence in a corticocerebellar network

The processing of visual and haptic inputs, occurring either separately or jointly, is crucial for everyday-life object recognition, and has been a focus of recent neuroimaging research. Previously, visuohaptic convergence has been mostly investigated with matching-task paradigms. However, much less is known about visuohaptic convergence in the absence of additional task demands. We conducted two functional magnetic resonance imaging experiments in which subjects actively touched and/or viewed unfamiliar object stimuli without any additional task demands. In addition, we performed two control experiments with audiovisual and audiohaptic stimulation to examine the specificity of the observed visuohaptic convergence effects. We found robust visuohaptic convergence in bilateral lateral occipital cortex and anterior cerebellum. In contrast, neither the anterior cerebellum nor the lateral occipital cortex showed any involvement in audiovisual or audiohaptic convergence, indicating that multisensory convergence in these regions is specifically geared to visual and haptic inputs. These data suggest that in humans the lateral occipital cortex and the anterior cerebellum play an important role in visuohaptic processing even in the absence of additional task demands

Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

Development of a Novel Renal Activity Index of Lupus Nephritis in Children and Young Adults

OBJECTIVE: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histologic LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n = 47) at the time of kidney biopsy. Histologic LN activity was measured by the National Institutes of Health activity index (NIH-AI) and the tubulointerstitial activity index (TIAI). High LN-activity status (versus moderate/low) was defined as NIH-AI scores >10 (versus ≤10) or TIAI scores >5 (versus ≤5). RAIL algorithms that predicted LN-activity status for both NIH-AI and TIAI were derived by stepwise multivariate logistic regression, considering traditional biomarkers and UBMs as candidate components. The accuracy of the RAIL for discriminating by LN-activity status was determined. RESULTS: The differential excretion of 6 UBMs (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin, and kidney injury molecule 1) standardized by urine creatinine was considered in the RAIL. These UBMs predicted LN-activity (NIH-AI) status with >92% accuracy and LN-activity (TIAI) status with >80% accuracy. RAIL accuracy was minimally influenced by concomitant LN damage. Accuracies between 71% and 85% were achieved without standardization of the UBMs. The strength of these UBMs to reflect LN-activity status was confirmed by principal component and linear discriminant analyses. CONCLUSION: The RAIL is a robust and highly accurate noninvasive measure of LN activity. The measurement properties of the RAIL, which reflect the degree of inflammatory changes as seen on kidney biopsy, will require independent validation

Identification of a Genomic Region Between SLC29A1 and HSP90AB1 Associated With Risk of Bevacizumab-Induced Hypertension: CALGB 80405 (Alliance)

Purpose: Bevacizumab is a VEGF-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of multiple cancers. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy or lead to cardiovascular complications. The factors that contribute to interindividual variability in blood pressure rise during bevacizumab treatment are not well understood.Experimental Design: To identify genomic regions associated with bevacizumab-induced hypertension risk, sequencing of candidate genes and flanking regulatory regions was performed on 61 patients treated with bevacizumab (19 cases developed early-onset grade 3 hypertension and 42 controls had no reported hypertension in the first six cycles of treatment). SNP-based tests for common variant associations and gene-based tests for rare variant associations were performed in 174 candidate genes.Results: Four common variants in independent linkage disequilibrium blocks between SLC29A1 and HSP90AB1 were among the top associations. Validation in larger bevacizumab-treated cohorts supported association between rs9381299 with early grade 3+ hypertension (P = 0.01; OR, 2.4) and systolic blood pressure >180 mm Hg (P = 0.02; OR, 2.1). rs834576 was associated with early grade 3+ hypertension in CALGB 40502 (P = 0.03; OR, 2.9). These SNP regions are enriched for regulatory elements that may potentially increase gene expression. In vitro overexpression of SLC29A1 in human endothelial cells disrupted adenosine signaling and reduced nitric oxide levels that were further lowered upon bevacizumab exposure.Conclusions: The genomic region between SLC29A1 and HSP90AB1 and its role in regulating adenosine signaling are key targets for further investigation into the pathogenesis of bevacizumab-induced hypertension