Nox2 redox signaling maintains essential cell populations in the brain.

Reactive oxygen species (ROS) are conventionally classified as toxic consequences of aerobic life, and the brain is particularly susceptible to ROS-induced oxidative stress and damage owing to its high energy and oxygen demands. NADPH oxidases (Nox) are a widespread source of brain ROS implicated in seizures, stroke and neurodegeneration. A physiological role for ROS generation in normal brain function has not been established, despite the fact that mice and humans lacking functional Nox proteins have cognitive deficits. Using molecular imaging with Peroxyfluor-6 (PF6), a new selective fluorescent indicator for hydrogen peroxide (H(2)O(2)), we show that adult hippocampal stem/progenitor cells (AHPs) generate H(2)O(2) through Nox2 to regulate intracellular growth signaling pathways, which in turn maintains their normal proliferation in vitro and in vivo. Our results challenge the traditional view that brain ROS are solely deleterious by demonstrating that controlled ROS chemistry is needed for maintaining specific cell populations

Second-generation PLINK: rising to the challenge of larger and richer datasets

PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.Comment: 2 figures, 1 additional fil

Constructing Cross-lingual Consumer Health Vocabulary with Word-Embedding from Comparable User Generated Content

The online health community (OHC) is the primary channel for laypeople to share health information. To analyze the health consumer-generated content (HCGC) from the OHCs, identifying the colloquial medical expressions used by laypeople is a critical challenge. The open-access and collaborative consumer health vocabulary (OAC CHV) is the controlled vocabulary for addressing such a challenge. Nevertheless, OAC CHV is only available in English, limiting its applicability to other languages. This research proposes a cross-lingual automatic term recognition framework for extending the English CHV into a cross-lingual one. Our framework requires an English HCGC corpus and a non-English (i.e., Chinese in this study) HCGC corpus as inputs. Two monolingual word vector spaces are determined using the skip-gram algorithm so that each space encodes common word associations from laypeople within a language. Based on the isometry assumption, the framework aligns two monolingual spaces into a bilingual word vector space, where we employ cosine similarity as a metric for identifying semantically similar words across languages. The experimental results demonstrate that our framework outperforms the other two large language models in identifying CHV across languages. Our framework only requires raw HCGC corpora and a limited size of medical translations, reducing human efforts in compiling cross-lingual CHV.Comment: accepted in the IEEE International Conference on Healthcare Informatics (IEEE ICHI 2024

Curl-Flow: Boundary-Respecting Pointwise Incompressible Velocity Interpolation for Grid-Based Fluids

We propose to augment standard grid-based fluid solvers with pointwise divergence-free velocity interpolation, thereby ensuring exact incompressibility down to the sub-cell level. Our method takes as input a discretely divergence-free velocity field generated by a staggered grid pressure projection, and first recovers a corresponding discrete vector potential. Instead of solving a costly vector Poisson problem for the potential, we develop a fast parallel sweeping strategy to find a candidate potential and apply a gauge transformation to enforce the Coulomb gauge condition and thereby make it numerically smooth. Interpolating this discrete potential generates a pointwise vector potential whose analytical curl is a pointwise incompressible velocity field. Our method further supports irregular solid geometry through the use of level set-based cut-cells and a novel Curl-Noise-inspired potential ramping procedure that simultaneously offers strictly non-penetrating velocities and incompressibility. Experimental comparisons demonstrate that the vector potential reconstruction procedure at the heart of our approach is consistently faster than prior such reconstruction schemes, especially those that solve vector Poisson problems. Moreover, in exchange for its modest extra cost, our overall Curl-Flow framework produces significantly improved particle trajectories that closely respect irregular obstacles, do not suffer from spurious sources or sinks, and yield superior particle distributions over time

Management of Elbow Dislocations in the National Football League.

Background: Although much literature exists regarding the treatment and management of elbow dislocations in the general population, little information is available regarding management in the athletic population. Furthermore, no literature is available regarding the postinjury treatment and timing of return to play in the contact or professional athlete. Purpose: To review the clinical course of elbow dislocations in professional football players and determine the timing of return to full participation. Study Design: Case series; Level of evidence, 4. Methods: All National Football League (NFL) athletes with elbow dislocations from 2000 through 2011 who returned to play during the season were identified from the NFL Injury Surveillance System (NFL ISS). Roster position, player activity, use of external bracing, and clinical course were reviewed. Mean number of days lost until full return to play was determined for players with elbow dislocations who returned in the same season. Results: From 2000 to 2011, a total of 62 elbow dislocations out of 35,324 injuries were recorded (0.17%); 40 (64.5%) dislocations occurred in defensive players, 12 (19.4%) were in offensive players; and 10 (16.1%) were during special teams play. Over half of the injuries (33/62, 53.2%) were sustained while tackling, and 4 (6.5%) patients required surgery. A total of 47 (75.8%) players who sustained this injury were able to return in the same season. For this group, the mean number of days lost in players treated conservatively (45/47) was 25.1 days (median, 23.0 days; range, 0.0-118 days), while that for players treated operatively (2/47) was 46.5 days (median, 46.5 days; range, 29-64 days). Mean return to play based on player position was 25.8 days for defensive players (n = 28; median, 21.5 days; range, 3.0-118 days), 24.1 days for offensive players (n = 11; median, 19 days; range, 2.0-59 days), and 25.6 days for special teams players (n = 8; median, 25.5 days; range, 0-44 days). Conclusion: Elbow dislocations comprise less than a half of a percent of all injuries sustained in the NFL. Most injuries occur during the act of tackling, with the majority of injured athletes playing a defensive position. Players treated nonoperatively missed a mean of 25.1 days, whereas those managed operatively missed a mean of 46.5 days

Chemistry and radiative shielding in star forming galactic disks

To understand the conditions under which dense, molecular gas is able to form within a galaxy, we post-process a series of three-dimensional galactic-disk-scale simulations with ray-tracing based radiative transfer and chemical network integration to compute the equilibrium chemical and thermal state of the gas. In performing these simulations we vary a number of parameters, such as the ISRF strength, vertical scale height of stellar sources, cosmic ray flux, to gauge the sensitivity of our results to these variations. Self-shielding permits significant molecular hydrogen (H2) abundances in dense filaments around the disk midplane, accounting for approximately ~10-15% of the total gas mass. Significant CO fractions only form in the densest, n>~10^3 cm^-3, gas where a combination of dust, H2, and self-shielding attenuate the FUV background. We additionally compare these ray-tracing based solutions to photochemistry with complementary models where photo-shielding is accounted for with locally computed prescriptions. With some exceptions, these local models for the radiative shielding length perform reasonably well at reproducing the distribution and amount of molecular gas as compared with a detailed, global ray tracing calculation. Specifically, an approach based on the Jeans Length with a T=40K temperature cap performs the best in regards to a number of different quantitative measures based on the H2 and CO abundances.Comment: 21 Pages, 15 figures. Submitted to MNRAS. Comments welcom

Magneto-optic Kerr effect in a spin-polarized zero-moment ferrimagnet

The magneto-optical Kerr effect (MOKE) is often assumed to be proportional to the magnetisation of a magnetically ordered metallic sample; in metallic ferrimagnets with chemically distinct sublattices, such as rare-earth transition-metal alloys, it depends on the difference between the sublattice contributions. Here we show that in a highly spin polarized, fully compensated ferrimagnet, where the sublattices are chemically similar, MOKE is observed even when the net moment is strictly zero. We analyse the spectral ellipsometry and MOKE of Mn 2 Ru x Ga, and show that this behaviour is due to a highly spin-polarized conduction band dominated by one of the two manganese sublattices which creates helicity-dependent reflectivity determined by a broad Drude tail. Our findings open new prospects for studying spin dynamics in the infra-red.Comment: 7 pages, 7 figure

Endogenous hydrogen peroxide production in the epithelium of the developing embryonic lens

Purpose Hydrogen peroxide (H2O2) is an endogenously produced reactive oxygen species (ROS) present in a variety of mammalian systems. This particular ROS can play dichotomous roles, being beneficial in some cases and deleterious in others, which reflects the level and location of H2O2 production. While much is known about the redox regulation of ROS by antioxidant and repair systems in the lens, little is known about the endogenous production of H2O2 in embryonic lens tissue or the physiologic relevance of endogenous H2O2 to lens development. This gap in knowledge exists primarily from a lack of reagents that can specifically detect endogenous H2O2 in the intact lens. Here, using a recently developed chemoselective fluorescent boronate probe, peroxyfluor-6 acetoxymethyl ester (PF6-AM), which selectively detects H2O2 over related ROS, we examined the endogenous H2O2 signals in the embryonic lens. Methods: Embryonic day 10 chick whole lenses in ex vivo organ culture and lens epithelial cells in primary culture were loaded with the H2O2 probe PF6-AM. To determine the relationship between localization of mitochondria with active membrane potential and the region of H2O2 production in the lens, cells were exposed to the mitochondrial probe MitoTracker Red CMXRos together with PF6-AM. Diphenyleneiodonium (DPI), a flavin inhibitor that blocks generation of intracellular ROS production, was used to confirm that the signal from PF6-AM was due to endogenous ROS production. All imaging was performed by live confocal microscopy. Results: PF6-AM detected endogenous H2O2 in lens epithelial cells in whole lenses in ex vivo culture and in lens epithelial cells grown in primary culture. No endogenous H2O2 signal could be detected in differentiating lens fiber cells with this probe. Treatment with DPI markedly attenuated the fluorescence signal from the peroxide-specific probe PF6-AM in the lens epithelium, suggesting that basal generation of ROS occurs in this region. The lens epithelial cells producing an endogenous H2O2 signal were also rich in actively respiring mitochondria. Conclusions: PF6-AM can be used as an effective reagent to detect the presence and localization of endogenous H2O2 in live lens cells

ABA Triblock Brush Polymers: Synthesis, Self-Assembly, Conductivity, and Rheological Properties

The synthesis, self-assembly, conductivity, and rheological properties of ABA triblock brush polymers (BBCPs) with grafted polystyrene (A block, N_(PS) = 21) and poly(ethylene oxide) (B block, N_(PEO) = 45) side chains are reported. Two backbone molecular weights (N_A:N_B:N_A = 11:78:11 and 15:119:15) were investigated with lithium bis(trifluoromethane)sulfonimide (LiTFSI) doping ratios 2 ≤ [EO]:[Li+] ≤ 20. Blends with 2 ≤ [EO]:[Li+] ≤ 10 suppress PEO crystallization and self-assemble into hexagonally packed cylinders of the minority gPS component. Conductivity is on the order of 10^(–3) S/cm at 105 °C with a corresponding elastic modulus ca. 10^4 Pa. The optimum conductivity occurs at a blend ratio near 10:1 [EO]:[Li+], similar to that reported for linear block copolymer analogues